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Lactoferrin induces autophagy in HK-2 cells. (A) Cell viability of lactoferrin-treated cells. Cells were treated with various concentrations of lactoferrin for 24 h. * p < 0.05 compared with control. (B) The protein levels of LC3 and beclin 1 in HK-2 cells treated with lactoferrin for 24 h. (C) Confocal immunofluorescence microscopy imaging of LC3 following 24 h treatment with lactoferrin. (D) Quantification of punctate LC3 staining. Cells were treated with various concentrations of lactoferrin for 24 h. * p < 0.05 compared with control. (E) Protein levels of Akt/mTOR and AMPK pathways. Cells were treated with various concentrations of lactoferrin for 24 h. (F) Western blotting for lactoferrin, LC3 and beclin 1 proteins derived from HK-2 cells without (vector control) or with LTF overexpression for 24 h.
Source publication
Patients with acute kidney injury (AKI) who survive the acute stage are at notable risk for chronic kidney disease (CKD) progression. There is no single therapy that can effectively prevent the AKI to CKD transition. Autophagy is a cytoplasmic component degradation pathway and has complex functions in several diseases, such as renal fibrosis. Previ...
Contexts in source publication
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... determine whether lactoferrin affects cell viability in HK-2 cells (a human kidney proximal tubular epithelial cell line), the cells were treated with lactoferrin at the indicated concentrations to analyze cell viability ( Figure 2A). The results showed that lactoferrin did not cause obvious changes in cell viability. ...
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... high concentrations (200 µg/mL and 400 µg/mL) of lactoferrin slightly increased the viability of HK-2 cells. Furthermore, we examined whether lactoferrin induced autophagy by measuring autophagy-associated proteins using western blot analysis ( Figure 2B). The levels of beclin 1 and LC3-II were markedly increased in cells treated with lactoferrin. ...
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... levels of beclin 1 and LC3-II were markedly increased in cells treated with lactoferrin. In addition, we determined the percentage of cells with punctate LC3 staining by fluorescence microscopy ( Figure 2C,D). The results found that treatment with lactoferrin caused a concentration-dependent increase in LC3 dots in HK-2 cells. ...
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... previous study reported that autophagy induction can be regulated by the activation of AMPK and inhibition of Akt/mTOR pathway [22]. As shown in Figure 2E, lactoferrin increased AMPK phosphorylation and inhibited Akt and mTOR phosphorylation. The overexpression of LTF could predominantly increase lactoferrin expression ( Figure 2F). ...
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... shown in Figure 2E, lactoferrin increased AMPK phosphorylation and inhibited Akt and mTOR phosphorylation. The overexpression of LTF could predominantly increase lactoferrin expression ( Figure 2F). Furthermore, forced expression of the exogenous LTF gene elevated beclin 1 and LC3-II expression. ...
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... determine whether lactoferrin affects cell viability in HK-2 cells (a human kidney proximal tubular epithelial cell line), the cells were treated with lactoferrin at the indicated concentrations to analyze cell viability (Figure 2A). The results showed that lactoferrin did not cause obvious changes in cell viability. ...
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... high concentrations (200 μg/mL and 400 μg/mL) of lactoferrin slightly increased the viability of HK-2 cells. Furthermore, we examined whether lactoferrin induced autophagy by measuring autophagy-associated proteins using western blot analysis ( Figure 2B). The levels of beclin 1 and LC3-II were markedly increased in cells treated with lactoferrin. ...
Context 8
... levels of beclin 1 and LC3-II were markedly increased in cells treated with lactoferrin. In addition, we determined the percentage of cells with punctate LC3 staining by fluorescence microscopy ( Figure 2C,D). The results found that treatment with lactoferrin caused a concentration-dependent increase in LC3 dots in HK-2 cells. ...
Context 9
... previous study reported that autophagy induction can be regulated by the activation of AMPK and inhibition of Akt/mTOR pathway [22]. As shown in Figure 2E, lactoferrin increased AMPK phosphorylation and inhibited Akt and mTOR phosphorylation. The overexpression of LTF could predominantly increase lactoferrin expression ( Figure 2F). ...
Context 10
... shown in Figure 2E, lactoferrin increased AMPK phosphorylation and inhibited Akt and mTOR phosphorylation. The overexpression of LTF could predominantly increase lactoferrin expression ( Figure 2F). Furthermore, forced expression of the exogenous LTF gene elevated beclin 1 and LC3-II expression. ...
Context 11
... histological structures with normal renal tubules and glomeruli were observed in the FA + LFH group. The assessment of renal fibrosis in kidneys by Masson's trichrome staining and immunohistochemical staining for profibrotic marker (α-SMA) showed significant renal fibrosis development in the FA group ( Figure 7B and Figure S2). Fibrosis was restrained in LF-treated mice in comparison to that in FA-treated mice. ...
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... the protective mechanisms of autophagy help repair and regenerate damaged kidneys [40]. In our current study, lactoferrin induced autophagy via the activation of AMPK and the inhibition of the Akt/mTOR pathway in HK-2 cells (Figure 2). The folic acid mouse model showed that the kidney sections of lactoferrin-treated mice markedly increased autophagy ( Figure 7C). ...
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Objective
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Citations
... When dosing animals with colostrum, it was noted that it is crucial in reducing the concentration of urea and creatinine. The reason for this may be due to colostrum containing lactoferrin, which plays a part in reducing the toxic effects of chemotherapy, eliminating oxidative stress, increasing autoimmunity, and preventing kidney fibrosis (Hsu et al., 2020;Mohammed et al., 2021). Another unsaturated material called lactoferrin can attach to cells, eliminate free iron radicals that oxidize lipids, and stifle free radicals that lead to urea and creatinine shortage (Superti, 2020). ...
Both radiation and chemotherapy are vital treatments for cancer patients, but they have some disadvantages, for example, a greater chance of adverse effects, limited accessibility, and the non-selective character of chemotherapy drugs. The current study's objective was to look at the function of different concentrations of bovine colostrum in enhancing and activating the immune system, reducing immune suppression, and mitigating the effects of the chemotherapy Etoposide on some physiological and immune parameters in male albino rats. Eight groups, consisting of the control group (C) and several treatment groups (T1-T7), were created from forty adult male rats. After a 4-week experimental period, the animals were anesthetized, and blood was directly drawn from the heart for necessary tests. The tests included blood tests (Red blood cell count, Hemoglobin concentration, packed cell volume PCV), immune parameters (C-reactive protein, Interleukin 12, platelet count), and tests for some liver and kidney parameters (Urea, Creatinine, ALT, AST, ALP). Additionally, antioxidant and oxidant tests (MDA, SOD, CAT, GLU) were conducted. According to the findings, the normal values of the parameters that were tested significantly changed when etoposide was used in group T1. However, the use of colostrum at different concentrations with Etoposide for groups T2, T3, and T4 resulted in improvement in the values of the measured parameters, approaching the control group in some cases, especially in group T4 exposed to a dose of colostrum and Etoposide of 1500 IU/kg. On the other hand, groups treated with colostrum alone (T5, T6, T7) indicated results similar to the group under control, and no unfavourable side effects were noticed. In conclusion, the use of chemotherapy Etoposide has negative effects on some physiological and hematological parameters and affects the vital functions of treated rats. Conversely, the study demonstrates the positive role of using colostrum at various concentrations in enhancing immunity and preventing or reducing oxidative stress and inflammation resulting from Etoposide on the vital functions of male albino rats.
... The antioxidative effects of lactoferrin as well as its protective effects in various renal pathologies have been demonstrated in a number of studies. These studies showed that lactoferrin administration reduced albuminuria, blood urea, and creatinine levels in the renal disease model, which implied improved renal function [234][235][236][237]. Alleviation of renal damage by lactoferrin was further demonstrated by the reduction of kidney injury markers and histological findings [234][235][236]. ...
... These studies showed that lactoferrin administration reduced albuminuria, blood urea, and creatinine levels in the renal disease model, which implied improved renal function [234][235][236][237]. Alleviation of renal damage by lactoferrin was further demonstrated by the reduction of kidney injury markers and histological findings [234][235][236]. Moreover, lactoferrin reduced inflammatory cytokine levels (e.g., IL-6), downregulated ERK1/2 and NF-κB pathways [236], and lowered CTGF levels [235,237], proving the anti-inflammatory and anti-fibrotic roles of lactoferrin. Notably, lactoferrin exerted antioxidative actions in its protection against renal diseases. ...
... Notably, lactoferrin exerted antioxidative actions in its protection against renal diseases. It was shown to decrease oxidative stress and enhance antioxidative capacity by upregulating the Nrf2/HO-1 pathway [235,237]. As oxidative damages caused by ROS were prevented, kidney injury and failure could be alleviated, associated with the reduced morbidity and mortality of CKD patients [238]. ...
Chronic kidney disease (CKD) presents a substantial global public health challenge, with high morbidity and mortality. CKD patients often experience dyslipidaemia and poor glycaemic control, further exacerbating inflammation and oxidative stress in the kidney. If left untreated, these metabolic symptoms can progress to end-stage renal disease, necessitating long-term dialysis or kidney transplantation. Alleviating inflammation responses has become the standard approach in CKD management. Medications such as statins, metformin, and GLP-1 agonists, initially developed for treating metabolic dysregulation, demonstrate promising renal therapeutic benefits. The rising popularity of herbal remedies and supplements, perceived as natural antioxidants, has spurred investigations into their potential efficacy. Notably, lactoferrin, Boerhaavia diffusa, Amauroderma rugosum, and Ganoderma lucidum are known for their anti-inflammatory and antioxidant properties and may support kidney function preservation. However, the mechanisms underlying the effectiveness of Western medications and herbal remedies in alleviating inflammation and oxidative stress occurring in renal dysfunction are not completely known. This review aims to provide a comprehensive overview of CKD treatment strategies and renal function preservation and critically discusses the existing literature’s limitations whilst offering insight into the potential antioxidant effects of these interventions. This could provide a useful guide for future clinical trials and facilitate the development of effective treatment strategies for kidney functions.
... Our former studies found that the lactoferrin treatments ameliorated the oxidative stress-related damage in mammalian cells [32,33] So far, a series of extensive studies on the biological properties and pharmacological consequences of lactoferrin have demonstrated that the bioactivities of lactoferrin benefit the nephroprotective effects of lactoferrin interventions against a variety of renal injuries induced by carfilzomib, cyclophosphamide, chromium, and ferric nitrilotriacetate, as well as acute kidney injuries by suppressing the oxidative stress-related damages [34][35][36]. However, the potential connection between the nephroprotective effect of lactoferrin intervention against arsenic-induced renal dysfunctions and the underlying molecular mechanisms related to the inhibition of oxidative stress-related damages remains unclear. ...
It is said that a wide range of renal functions are at risk from arsenic exposure. We examined how lactoferrin administration may mitigate inflammation, apoptosis, redox imbalance, and fibrosis in order to counteract arsenic-induced nephrotoxicity. Accordingly, male C57BL/6 mice (6 weeks) were divided into six experimental groups with six mice in each group. The first and second groups were intragastrically administered normal saline and sodium arsenite (NaAsO2) at 5 mg/kg body weight concentrations as the negative control (NC) and NaAsO2 groups. The third, fourth, and fifth groups were intragastrically administered lactoferrin at concentrations of 100, 200, and 400 mg/kg body weight in addition to NaAsO2 at concentrations of 5 mg/kg body weight. The sixth group was intragastrically administered lactoferrin at a concentration of 200 mg/kg body weight with the experimental group set as the lactoferrin group. After daily drug administration for 4 weeks, the lactoferrin concentrations were optimized based on the results of renal index and renal function. Histopathological, biochemical, and gene expression analyses were performed to evaluate the status of renal tissue architecture, redox imbalance, inflammation, apoptosis, and fibrosis to confirm the alleviative effect of lactoferrin treatment against the NaAsO2 exposure-induced nephrotoxicity. The results confirmed that the 200 mg/kg lactoferrin treatment mitigated these arsenic effects and maintained the normal renal frameworks. Conclusively, disrupting the renal redox balance and triggering inflammation, apoptosis, along with fibrosis is a milieu that arsenic, robustly exerts its nephrotoxic effect. Lactoferrin, probably by its direct and indirect control mechanism on these said pathways, can mitigate the nephrotoxicity and preserve the normal renal health.
... Furthermore, the single administration of Coq 10 and LF noticeably reduced oxidative stress. These findings are in consistent with the previous studies on the antioxidative activities of Coq 10 and LF [53,54]. ...
Background
Hepatorenal syndrome is a life-threatening medical complication of liver cirrhosis. Hepatic cirrhosis is commonly accompanied by rapid failure of renal functions. Thioacetamide (TAA) is a potent hepatotoxin and a class 2-type carcinogen. Ubiquinone (Coq 10 ) and lactoferrin (LF) are potent antioxidants with antifibrotic and antiinflammatory effects. However, whether Coq 10 and LF reduce the hepatorenal injury induced by TAA remains unclear. Here, we investigated the potential protective effect of both/or Coq 10 and LF in ameliorating TAA-induced hepatorenal injury and the role of WNT4 gene expression in detecting TAA-induced renal injury in rats. Seventy healthy and mature male Sprague Dawley rats, weighting (200 g ± 20 g) and aging (4–6) weeks were randomly divided into seven groups ( n = 10): control, Coq 10 , LF, TAA, TAA + Coq 10 , TAA + LF, and TAA + Coq 10 + LF. The hepatorenal injury was induced through intraperitoneal (i.p.) injection of TAA (150 mg/kg/twice/weekly) for nine weeks. Coq 10 (10 mg/kg/day) and LF (200 mg/kg/day) were orally administered for nine weeks.
Results
TAA induced marked hepatorenal damage, evident by the significant increase in the alanine aminotransferase (ALT), aspartate transaminase (AST), serum creatinine (SCr) activities, and the blood urea nitrogen (BUN) level. Besides, the significant increases in concentrations of malondialdehyde (MDA) and nitric oxide (NOx) together with significant decreases in the activities of catalase (CAT) and superoxide dismutase (SOD). The histopathological analysis of the TAA group showed obvious fibrosis, steatosis, and inflammation of the hepatic parenchyma as well as severe glomerular and tubular damage of the renal parenchyma. In addition, TAA induced marked ultrastructural alterations and up-regulation in the expression of the WNT4 gene in the kidney. Meanwhile, the biochemical, histopathological, and ultrastructural alterations were significantly decreased with significant down-regulation in the expression of WNT4 in the groups exposed to TAA and treated with Coq 10 and LF.
Conclusion
Our data suggested that Coq 10 and LF could have protective effects on TAA hepatorenal damage, through improving the hepatic and renal functions, reduction of oxidative stress, structural and ultrastructural alterations, besides down-regulation in the expression of WNT4.
... Autophagy has recently been shown to play an important role in the pathogenesis of diabetic complications, and improving cardiac function and myocardial fibrosis by interfering with autophagic activity holds potential as a novel approach to the treatment of cardiac complications of T2DM [16,17]. Treatment options for T2DM that lower both glucose and lipid levels along with exhibiting an antioxidant effect are expected to break the vicious cycle formed by oxidative stress and disorders of glucose metabolism. ...
... After injection of LTF, the positive liver stove area of hepatitis rats decreased, which inhibited the progress of hepatitis and liver fibrosis through downgrading TGF-β1, TNF-α and COL1A1 [30]. Similarly, LTF decreased the phosphorylation of Akt and mTOR and the expression of CTGF and TGF-β1 to inhibit renal fibrosis [31]. ...
Background:With the mounting number of intrauterine operations, the incidence of intrauterine adhesion continues to rise. However, the specific pathogenesis of intrauterine adhesion has not been clear and there is no fundamental treatment so far. Objective:IUA is an endometrial fibrosis illness that gravely jeopardizes the reproductive health of women of reproductive age. We elucidated the pathogenesis of IUA at the protein level to provide a more effective research basis for diagnosis and treatment. Methods: This study collected 15 endometrial tissue samples and divided them into three comparison groups (Adhesion/Control group, Endometrium/Adhesion group, and Endometrium/Control group). Label-free quantitative proteomics was used to identify differentially expressed proteins and performed a comprehensive bioinformatics analysis. The research was followed by a quantitative analysis of selected target proteins using a parallel reaction monitoring method. Results: 1328, 290, and 1335 differential proteins were found in each comparison group. Many features of the differential proteins were also identified by GO enrichment analysis and KEGG pathways analysis. Parallel reaction monitoring analysis was performed to quantify 14 target proteins (PGM5, CAMK2G, ABHD6, MYLK, SYNPO2, LTF, PTPN11, TGF-β1, SLC4A1, PROS1, IRAG1, ADIPOQ, HLA-DRB3, COQ6). Among them, TGF-β1 was previously reported as a significant protein in intrauterine adhesion, while other proteins were newly discovered. Conclusions: These proteins are anticipated to develop as biomarkers for intrauterine adhesion and have a specific role in diagnosis and therapy.
... Considerable evidence has shown that LTF and LYZ have important anti oxida nt, anti-in fl a m m a t o r y a n d nephroprotective activities (41-43). LTF inhibits TGF-b1-induced renal fibrosis by restraining the expression of the profibrogenic genes CTGF, PAI-1 and collagen I (44). PLTP not only influences lipid transfer and lipoprotein metabolism, which is associated with cardio-metabolic diseases (45), but also plays a key role in the modulation of adaptive immune functions through alternation of T cell helper polarization (46). ...
Background
Chronic kidney disease (CKD) is the third-leading cause of premature mortality worldwide. It is characterized by rapid deterioration due to renal interstitial fibrosis (RIF) via excessive inflammatory infiltration. The aim of this study was to discover key immune-related genes (IRGs) to provide valuable insights and therapeutic targets for RIF in CKD.
Materials and methods
We screened differentially expressed genes (DEGs) between RIF samples from CKD patients and healthy controls from a public database. Least absolute shrinkage and selection operator regression analysis and receiver operating characteristic curve analysis were applied to identify significant key biomarkers. The single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to analyze the infiltration of immune cells between the RIF and control samples. The correlation between biomarkers and immune cell composition was assessed.
Results
A total of 928 DEGs between CKD and control samples from six microarray datasets were found, 17 overlapping immune-correlated DEGs were identified by integration with the ImmPort database, and six IRGs were finally identified in the model: apolipoprotein H (APOH), epidermal growth factor (EGF), lactotransferrin (LTF), lysozyme (LYZ), phospholipid transfer protein (PLTP), and secretory leukocyte peptidase inhibitor (SLPI). Two additional datasets and in vivo experiments indicated that the expression levels of APOH and EGF in the fibrosis group were significantly lower than those in the control group, while the expression levels of LTF, LYZ, PLTP, and SLPI were higher (all P < 0.05). These IRGs also showed a significant correlation with renal function impairment. Moreover, four upregulated IRGs were positively associated with various T cell populations, which were enriched in RIF tissues, whereas two downregulated IRGs had opposite results. Several signaling pathways, such as the “T cell receptor signaling pathway” and “positive regulation of NF-κB signaling pathway”, were discovered to be associated not only with immune cell infiltration, but also with the expression levels of six IRGs.
Conclusion
In summary, six IRGs were identified as key biomarkers for RIF, and exhibited a strong correlation with various T cells and with the NF-κB signaling pathway. All these IRGs and their signaling pathways may evolve as valuable therapeutic targets for RIF in CKD.
... 34 Lactoferrin also demonstrates reno-protective effects in CKD through reduction of inflammation, oxidative stress, apoptosis and renal fibrosis, and induction of autophagy and mitochondrial biogenesis in the kidneys. 35,36 In human kidney proximal tubular cells, lactoferrin induces autophagy through activating the AMP-activated protein kinase (AMPK) and inhibiting the Akt/mTOR pathways. 36 In patients with CKD, the level of proinflammatory cytokines such as IL-6 and TNF-α are elevated. ...
... 35,36 In human kidney proximal tubular cells, lactoferrin induces autophagy through activating the AMP-activated protein kinase (AMPK) and inhibiting the Akt/mTOR pathways. 36 In patients with CKD, the level of proinflammatory cytokines such as IL-6 and TNF-α are elevated. 37 The increase in the levels of inflammatory markers such as IL-6 in patients with CKD is observed due to oxidative stress, chronic inflammation, fluid overload, and decreased clearance of IL-6 associated with impaired renal function. ...
Background
Anemia occurs in majority of patients with chronic kidney disease despite adequate dialysis and iron replete status. This study was done to evaluate the effects of lactoferrin with or without iron supplementation for the treatment of anemia in patients with chronic kidney disease (CKD).
Methods
In this prospective, observational, single-center, single-arm pilot study, adult patients aged >18 years, having stage 5 CKD (estimated glomerular filtration rate [eGFR] <15 ml/min/1.73 m ² ), and who had anemia (hemoglobin [Hb] <10 g/dl; transferrin saturation [T sat ] >20%) were included. Patients were treated with 100 mg of oral lactoferrin twice a day for one month with or without iron supplementation. Patients had been on stable erythropoietin doses for ≥1 month prior to inclusion in the study. We report on the improvement in Hb levels and effect on inflammatory markers from baseline at four weeks.
Results
A total of 46 CKD patients having anemia were included. Patients had a mean age of 39.3 years, and a majority were men (69.6%). Improvement in the mean (SD) Hb level (g/dl) was observed from baseline (8.18 [1.19]) to Week 2 (8.54 [1.57]), which attained significance at Week 4 (8.96 [1.93]; P < 0.001; mean difference: −0.76; 95% confidence interval [CI]: −1.291 to − 0.2383). The improvement in Hb was higher in women than in men ( P = 0.48) and in patients receiving lactoferrin with iron supplementation than in those receiving lactoferrin alone ( P = 0.14). There was a non-significant decrease in the erythrocyte sedimentation rate ( P = 0.14) and a non-significant increase in C-reactive protein ( P = 0.54) level.
Conclusions
Oral lactoferrin therapy was effective in improving hemoglobin levels in patients with advanced CKD and anemia. The effects of lactoferrin therapy on inflammatory markers remain uncertain.
... Lactoferrin (Ltf), known as an iron-binding glycoprotein, is the most abundant element in milk [14]. Prior research has illustrated that Ltf bears multi-pharmacological properties, including protection against infection, regulation inflammatory response, antioxidant and antifibrotic process [15][16][17][18]. Moreover, clinical trials have identified the safety of oral administration of bovine Ltf, and demonstrated the efficacy of Ltf on anti-infection, treatment of inflammation, cancer, metabolic disorders [17,[19][20][21]. ...
... In this study, we show that Ltf can restrain cardiac fibrosis, alleviate cardiac remodeling, and improve cardiac function through suppressing mTORC1/S6K/eIF-4B signaling pathway post MI in mice (Figure 8). Previous studies have expanded the value of Ltf in pathophysiological functions referring to regulation of metabolism, inflammation, apoptosis process and oxidative stress in various disorders [15,17,18]. To our knowledge, this is the first report to illustrate the protective effects of Ltf on MI injury. ...
... Prior study has demonstrated Ltf contributes protective effects on acute kidney injury and renal fibrosis [15]. Our gain-function study of Ltf via exogenous supplementation suggested that Ltf could alleviate detrimental cardiac remodeling, reduce fibrosis, and improve cardiac function after MI injury. ...
Rationale: Myocardial infarction (MI) causes a severe injury response that eventually leads to adverse cardiac remodeling and heart failure. Lactoferrin (Ltf), as a secreted protein, bears multi-pharmacological properties. Present study aims to establish the cardioprotective function and corresponding mechanism of Ltf in MI process.
Methods and results: We performed proteomic analysis in Tregs derived from MI heart, and identified Ltf as a remarkably upregulated secreted protein. However, Ltf was decreased in circulation and positively correlated with cardiac function both in mice and patients after MI. Ltf administration remarkably alleviated cardiac fibrosis and remodeling, improved cardiac function, and reduced incidence of heart failure in mice post-MI. In vitro, Ltf suppressed fibroblast to myofibroblast conversion induced by transforming growth factor-β (TGF-β). Mechanistically, phosphoproteomic landscape analysis revealed that Ltf repressed the activation of mTORC1/S6K/eIF-4B signaling pathway via interaction with CD74 receptor. Administration of mTORC1/S6K/eIF-4B axis agonist MHY1485 abolished the cardioprotective effects of Ltf. Besides, MHY1485 also markedly reversed the effects of Ltf on suppressing the transformation of fibroblast to myofibroblast mediated by TGF-β.
Conclusion: Our study established the cardiac protective role of Ltf in attenuating cardiac remodeling and improving cardiac function by inhibiting the activation of myofibroblasts through suppressing mTORC1/S6K/eIF-4B signaling pathway post-MI. Treatment with Ltf may serve as a potential novel therapeutic intervention in patients with MI.
... LF increases the cytotoxicity of natural killer cells in vitro while inhibiting the release of reactive oxygen species (ROS) from leukocytes at sites of inflammation, however, its antioxidant capacity decreases with decreasing iron saturation (Cutone et al., 2020a). LF inhibited oxidative stress-induced cell death and apoptosis by enhancing autophagy (Hsu et al., 2020). It is worth noting that, compare to holo-LF, apo-LF had a more pronounced stimulatory effect on the proliferation of crypt cells associated with inflammation in colon cancer (Fan et al., 2022). ...
