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Colitis-associated cancer (CAC) is a subtype of colon cancer that is driven by chronic inflammation and is prevalent in chronic ulcerative colitis patients. The development of CAC is associated with the inflammation-dysplasia-carcinoma pathway which is significantly different than adenoma-carcinoma pathway of sporadic colon cancer (CRC). Matrix Met...
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... healthy epithelium escalates CAC progression 22,23 . To investigate the role of MMP9 in preventing the loss of healthy epithelium, crypts were extracted from TgM9 and WT littermates' mice on Matrigel (as described in the Method section) and were used as an ex vivo model. The crypts growing into the colonoids were followed for days 2, 4, 7, and 9 (Fig. 5a, i-iv respectively). Crypts isolated from TgM9 mice differentiated faster (Fig. 5a-ii) and proliferated earlier ( Fig. 5a-iii and Fig. 5a-iv) to form the colonoids compared to the crypts isolated from the WT littermates. WB was also performed to assess the differentiation and proliferation. Figure 5b-i showed higher protein levels of ...
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... in preventing the loss of healthy epithelium, crypts were extracted from TgM9 and WT littermates' mice on Matrigel (as described in the Method section) and were used as an ex vivo model. The crypts growing into the colonoids were followed for days 2, 4, 7, and 9 (Fig. 5a, i-iv respectively). Crypts isolated from TgM9 mice differentiated faster (Fig. 5a-ii) and proliferated earlier ( Fig. 5a-iii and Fig. 5a-iv) to form the colonoids compared to the crypts isolated from the WT littermates. WB was also performed to assess the differentiation and proliferation. Figure 5b-i showed higher protein levels of carbonic anhydrase-1 (CA1) 24 , which is an enterocyte marker among TgM9 mice ...
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... crypts were extracted from TgM9 and WT littermates' mice on Matrigel (as described in the Method section) and were used as an ex vivo model. The crypts growing into the colonoids were followed for days 2, 4, 7, and 9 (Fig. 5a, i-iv respectively). Crypts isolated from TgM9 mice differentiated faster (Fig. 5a-ii) and proliferated earlier ( Fig. 5a-iii and Fig. 5a-iv) to form the colonoids compared to the crypts isolated from the WT littermates. WB was also performed to assess the differentiation and proliferation. Figure 5b-i showed higher protein levels of carbonic anhydrase-1 (CA1) 24 , which is an enterocyte marker among TgM9 mice derived colonoids on day 4 and day 9 compared ...
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... were extracted from TgM9 and WT littermates' mice on Matrigel (as described in the Method section) and were used as an ex vivo model. The crypts growing into the colonoids were followed for days 2, 4, 7, and 9 (Fig. 5a, i-iv respectively). Crypts isolated from TgM9 mice differentiated faster (Fig. 5a-ii) and proliferated earlier ( Fig. 5a-iii and Fig. 5a-iv) to form the colonoids compared to the crypts isolated from the WT littermates. WB was also performed to assess the differentiation and proliferation. Figure 5b-i showed higher protein levels of carbonic anhydrase-1 (CA1) 24 , which is an enterocyte marker among TgM9 mice derived colonoids on day 4 and day 9 compared to the colonoids ...
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... was also performed to assess the differentiation and proliferation. Figure 5b-i showed higher protein levels of carbonic anhydrase-1 (CA1) 24 , which is an enterocyte marker among TgM9 mice derived colonoids on day 4 and day 9 compared to the colonoids derived from WT littermates' mice. Figure 5b-ii indicated increased protein levels of the proliferation marker PCNA 25 on days 4 and 7 among TgM9 mice derived colonoids. ...
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... 5b-i showed higher protein levels of carbonic anhydrase-1 (CA1) 24 , which is an enterocyte marker among TgM9 mice derived colonoids on day 4 and day 9 compared to the colonoids derived from WT littermates' mice. Figure 5b-ii indicated increased protein levels of the proliferation marker PCNA 25 on days 4 and 7 among TgM9 mice derived colonoids. Interestingly, WB data showed that once colonoids were completely differentiated and proliferated, PCNA expression went down among TgM9 mice derived colonoids compared to WT littermates' mice ( Fig. 5b-ii). ...
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... littermates' mice. Figure 5b-ii indicated increased protein levels of the proliferation marker PCNA 25 on days 4 and 7 among TgM9 mice derived colonoids. Interestingly, WB data showed that once colonoids were completely differentiated and proliferated, PCNA expression went down among TgM9 mice derived colonoids compared to WT littermates' mice ( Fig. 5b-ii). Figure 5b-iii showed increased expression of selenoprotein P (SEPP1) an antioxidant marker 26 among the TgM9 mice derived colonoids compared to WT littermates' mice for days 4, 7, and 9 respectively. Densitometry analysis has been shown in Supplementary Fig. 5. Immunofluorescence staining for PCNA ( Fig. 5c-i, top panel) indicated ...
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... WB data showed that once colonoids were completely differentiated and proliferated, PCNA expression went down among TgM9 mice derived colonoids compared to WT littermates' mice ( Fig. 5b-ii). Figure 5b-iii showed increased expression of selenoprotein P (SEPP1) an antioxidant marker 26 among the TgM9 mice derived colonoids compared to WT littermates' mice for days 4, 7, and 9 respectively. Densitometry analysis has been shown in Supplementary Fig. 5. Immunofluorescence staining for PCNA ( Fig. 5c-i, top panel) indicated more PCNA positive cells among four days old colonoids derived from TgM9 mice compared to WT littermates' mice, supporting the WB data. ...
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... 5b-iii showed increased expression of selenoprotein P (SEPP1) an antioxidant marker 26 among the TgM9 mice derived colonoids compared to WT littermates' mice for days 4, 7, and 9 respectively. Densitometry analysis has been shown in Supplementary Fig. 5. Immunofluorescence staining for PCNA ( Fig. 5c-i, top panel) indicated more PCNA positive cells among four days old colonoids derived from TgM9 mice compared to WT littermates' mice, supporting the WB data. ...
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... compared to WT littermates' mice ( Fig. 5b-ii). Figure 5b-iii showed increased expression of selenoprotein P (SEPP1) an antioxidant marker 26 among the TgM9 mice derived colonoids compared to WT littermates' mice for days 4, 7, and 9 respectively. Densitometry analysis has been shown in Supplementary Fig. 5. Immunofluorescence staining for PCNA ( Fig. 5c-i, top panel) indicated more PCNA positive cells among four days old colonoids derived from TgM9 mice compared to WT littermates' mice, supporting the WB data. Similarly, immunofluorescence staining for SEPP1 (Fig. 5c-ii, bottom panel) indicated higher SEPP1 expression among four days old colonoids derived from TgM9 mice compared to WT ...
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... days 4, 7, and 9 respectively. Densitometry analysis has been shown in Supplementary Fig. 5. Immunofluorescence staining for PCNA ( Fig. 5c-i, top panel) indicated more PCNA positive cells among four days old colonoids derived from TgM9 mice compared to WT littermates' mice, supporting the WB data. Similarly, immunofluorescence staining for SEPP1 (Fig. 5c-ii, bottom panel) indicated higher SEPP1 expression among four days old colonoids derived from TgM9 mice compared to WT littermates' mice. The ex vivo data with colonoids imply that MMP9 plays a role in maintaining the differentiation and proliferation of crypts in colonic ...
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... figure on previous page) Fig. 5 MMP9 expression promotes epithelial cells differentiation and proliferation. a Crypts isolated from the colons of TgM9 and their WT littermates' mice were grown to form colonoids on Matrigel in 24 well plates. Colonoid formation was observed and images were captured on (i) day 2, (ii) day 4, (iii) day 7 at ×20 magnification, and (iv) ...
Citations
... [44] Studies have indicated that MMP9 expression is a natural biological means to inhibit CAC by restricting reactive oxygen species (ROS) accumulation and DNA damage in the colon. [45] The MYC gene encodes a transcription factor protein, which plays a role in regulating important processes such as cell growth, proliferation and apoptosis. [46] Studies have shown that the abnormal expression of MYC is closely linked to the development and prognosis of CRC, with high levels of MYC associated with increased tumor aggressiveness and metastasis. ...
The objective of this study was to investigate the potential targets and mechanism of Rheum palmatum L in the treatment of colorectal cancer based on the network pharmacology and molecular docking, which could provide the theoretical basis for clinical applications. The potential components were screened using TCMSP database and articles. The gene targets of colorectal cancer were screened through the Genecards database and Online Mendelian Inheritance in Man database. Then, the common targets of components and colorectal cancer were used to construct the network diagram of active components and targets in Cytoscape 3.7.0. The protein-protein interaction (PPI) diagram was generated using String database, and the targets were further analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes. Molecular docking between gene targets and active components was analyzed via AutoDock, and visualized through PyMol. Among this study, main targets might be TP53, EGF, MYC, CASP3, JUN, PTGS2, HSP90AA1, MMP9, ESR1, PPARG. And 10 key elements might associate with them, such as aloe-emodin, beta-sitosterol, gallic acid, eupatin, emodin, physcion, cis-resveratrol, rhein, crysophanol, catechin. The treatment process was found to involve nitrogen metabolism, p53 signaling pathway, and various cancer related pathway, as well as the AGE-RAGE signaling pathway, estrogen signaling pathway, interleukin-17 signaling pathway and thyroid hormone signaling pathway. The molecular docking was verified the combination between key components and their respective target proteins. Network pharmacological analysis demonstrated that R palmatum was could regulated p53, AGE-RAGE, interleukin-17 and related signaling pathway in colorectal cancer, which might provide a scientific basis of mechanism.
... Studies on MMP-9 deficient mice also suggest that MMP-9 is associated with mucosal damage in the early stages of colitis 48 . However, it has also been reported that MMP-9 restricts the accumulation of reactive oxygen species and DNA damage in colon, and thus inhibits the occurrence colitis-associated cancer 49 . Therefore, understanding the role of MMP-9 in UC and colitis-associated cancer is of great importance for exploring the treatment of UC and colitis-associated cancer. ...
Ulcerative colitis (UC) is a chronic, recurrent inflammatory bowel disease. UC confronts with severe challenges including the unclear pathogenesis and lack of specific diagnostic markers, demanding for identifying predictive biomarkers for UC diagnosis and treatment. We perform immune infiltration and weighted gene co-expression network analysis on gene expression profiles of active UC, inactive UC, and normal controls to identify UC related immune cell and hub genes. Neutrophils, M1 macrophages, activated dendritic cells, and activated mast cells are significantly enriched in active UC. MMP-9, CHI3L1, CXCL9, CXCL10, CXCR2 and S100A9 are identified as hub genes in active UC. Specifically, S100A9 is significantly overexpressed in mice with colitis. The receiver operating characteristic curve demonstrates the excellent performance of S100A9 expression in diagnosing active UC. Inhibition of S100A9 expression reduces DSS-induced colonic inflammation. These identified biomarkers associated with activity in UC patients enlighten the new insights of UC diagnosis and treatment.
... reactive oxygen species (ROS) (118,119). MMP-9 most likely mediates enterocyte apoptosis and proliferation by activating Notch-1, a transcription factor which gatekeeps the differentiation of goblet cells and, in turn, activates the tumor suppressor p53 (120). In multiple models, inhibiting this pathway leads to increased tumor number and grade. ...
Colorectal cancer (CRC) remains a major cause of morbidity and mortality. Therapeutic approaches for advanced CRC are limited and rarely provide long-term benefit. Enzymes comprising the 24-member matrix metalloproteinase (MMP) family of zinc- and calcium-dependent endopeptidases are key players in extracellular matrix degradation, a requirement for colon tumor expansion, invasion, and metastasis; hence, MMPs are an important research focus. Compared to sporadic CRC, less is known regarding the molecular mechanisms and the role of MMPs in the development and progression of colitis-associated cancer (CAC) − CRC on a background of chronic inflammatory bowel disease (IBD) − primarily ulcerative colitis and Crohn’s disease. Hence, the potential of MMPs as biomarkers and therapeutic targets for CAC is uncertain. Our goal was to review data regarding the role of MMPs in the development and progression of CAC. We sought to identify promising prognostic and therapeutic opportunities and novel lines of investigation. A key observation is that since MMPs may be more active in early phases of CAC, using MMPs as biomarkers of advancing neoplasia and as potential therapeutic targets for adjuvant therapy in those with advanced stage primary CAC rather than overt metastases may yield more favorable outcomes.
... Numerous studies have demonstrated abnormal expression of MMP2 and MMP9 in tissues following tumor occurrence [31]. Research has also revealed that MMP9 is a crucial regulator of the extracellular matrix and basement membrane, with its expression promoting the differentiation and proliferation of epithelial cells [22,32]. Moreover, MMP activity has been implicated in cancer progression [33]. ...
Background:
Glioma is one of the most aggressive malignant brain tumors and is characterized by invasive growth and poor prognosis. TBC1D1, a member of the TBC family, is associated with the development of various malignancies. However, the role of TBC1D1 in glioma-genesis remains unclear.
Methods:
The effect of TBC1D1 on the prognosis of glioma patients and related influencing factors were analyzed in the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. Expression of TBC1D1 in glioma cell lines was detected by western blotting. Cell viability and proliferation were measured by EdU and Colony formation assays, respectively. Transwell and wound healing assays were performed to determine the cell migration and invasion capacities. Immunofluorescence was used to observe actin morphology in the cytoskeleton.
Results:
We discovered that high TBC1D1 expression in gliomas led to poor prognosis. Downregulation of TBC1D1 in glioma cells significantly inhibited multiple important functions, such as proliferation, migration, and invasion. We further demonstrated that the tumor-inhibitory effect of TBC1D1 might occur through the P-LIMK/cofilin pathway, destroying the cytoskeletal structure and affecting the depolymerization of F-actin, thereby inhibiting glioma migration.
Conclusion:
TBC1D1 affects the balance and integrity of the actin cytoskeleton via cofilin, thereby altering the morphology and aggressiveness of glioma cells. This study provides a new perspective on its role in tumorigenesis, thereby identifying a potential therapeutic target for the treatment of gliomas.
... This suggests that the expression of MMP-9 is a natural biological way to inhibit CRC by limiting ROS accumulation and colonic DNA damage. Therefore, inhibition of MMP-9 may be harmful to patients with CRC [76]. Results indicate that MMP-9 has a protective host effect in CRC. ...
More than 90% of malignancies being squamous cell carcinoma originates from the oral mucosa and oral cancer is one of the most prevelant cancer worldwide. Candida species are common members of the oral microflora and are generally being regarded as commensals. However, they are able to cause a range of opportunistic infections and suggest a link between the presence of candida albicans in the oral cavity and development of Oral squamous cell carcinoma (OSCC). Candida species has been fundamentally linked to Cancereous processes as that takes advantage of the iumunosuppressed state of patients, particularly after Chemotherapy. However, this review will focus on the growing strength of the evidence that the Candida albicans is capable of promoting Cancer by several mechanisms: production of carcinogenic by products, triggering of Inflammation, induction of Th17 response, molecular mimicry that may be able to favour the Cancer development and dissemination. We underline the need not only to control this type of infection during Cancer treatment but also to find new therapeutic approaches to avoid the pro-tumour effect of this fungal species.
... These results indicated that NLRP3 is a crucial upstream of MMP9 and positively regulated MMP9 in VSMCs [43]. More importantly, the production of ROS exhibited enhanced expression and activity of MMP9 in osteoporosis, aortic dissection and cancer [44][45][46]. We further showed that the expression levels of 8-OHdG, NLRP3 and MMP9 were not only positively correlated, but also the interaction between them was confirmed by immunoprecipitation. ...
Reactive Oxygen Species (ROS) are widely accepted as a pernicious factor in the progression of intracranial aneurysm (IA), which is eminently related to cell apoptosis and extracellular matrix degradation, but the mechanism remains to be elucidated. Recent evidence has identified that enhancement of Cyclophilin D (CypD) under stress conditions plays a critical role in ROS output, thus accelerating vascular destruction. However, no study has confirmed whether cypD is a detrimental mediator of cell apoptosis and extracellular matrix degradation in the setting of IA development. Our data indicated that endogenous cypD mRNA was significantly upregulated in human IA lesions and mouse IA wall, accompanied by higher level of ROS, MMPs and cell apoptosis. CypD−/− remarkably reversed vascular smooth muscle cells (VSMCs) apoptosis and elastic fiber degradation, and significantly decreased the incidence of aneurysm and ruptured aneurysm, together with the downregulation of ROS, 8-OHdG, NLRP3 and MMP9 in vivo and vitro. Furthermore, we demonstrated that blockade of cypD with CsA inhibited the above processes, thus preventing IA formation and rupture, these effects were highly dependent on ROS output. Mechanistically, we found that cypD directly interacts with ATP5B to promote ROS release in VSMCs, and 8-OHdG directly bind to NLRP3, which interacted with MMP9 to increased MMP9 level and activity in vivo and vitro. Our data expound an unexpected role of cypD in IA pathogenesis and an undescribed 8-OHdG/NLRP3/MMP9 pathway involved in accelerating VSMCs apoptosis and elastic fiber degradation. Repressing ROS output by CypD inhibition may be a promising therapeutic strategy for prevention IA development.
... These enzymes play a pivotal role in various physiological and pathological processes, including morphogenesis, wound healing, and inflammation [16]. While MMP9 is undetectable in healthy tissues, its expression is significantly up-regulated in inflammation or cancer [17]. MMP9 can impede wound healing by degrading the extracellular matrix associated with normal tissue remodeling [18]. ...
Background
To investigate the role of neutrophils in corneal nerve regeneration.
Methods
A mouse model simulating corneal nerve injury was established and samples from corneal scraping with and without neutrophil closure were collected. These samples were used for corneal nerve staining, ribonucleic acid sequencing, and bioinformatics. Differential expression analysis was used to perform enrichment analysis to identify any significant differences between these two groups. The differential genes were then intersected with neutrophil-associated genes and a protein-protein interaction network was constructed using the intersected genes. The immune infiltration between the two groups was examined along with the immune cell variation between the high and low gene expression groups.
Results
Neutrophil removal delays corneal epithelial and nerve regeneration. A total of 546 differential genes and 980 neutrophil-associated genes, with 27 genes common to both sets were obtained. Molecular Complex Detection analysis yielded five key genes, namely integrin subunit beta 2 (ITGB2), matrix metallopeptidase 9 (MMP9), epidermal growth factor (EGF), serpin family E member 1 (SERPINE1), and plasminogen activator urokinase receptor (PLAUR). Among these genes, ITGB2, SERPINE1, and PLAUR exhibited increased expression in the neutrophil-confined group, while MMP9 and EGF showed decreased expression, with MMP9 and EGF displaying a more significant difference. Immune infiltration was also observed between the two groups, revealing significant differences in the infiltration of M0 macrophages, activated mast cells, and neutrophils. Moreover, the neutrophil levels were lower in the groups with low MMP9 and EGF expressions and higher in the high-expression group.
Conclusion
Neutrophil confinement might significantly affect the MMP9 and EGF expression levels. Strategies to inhibit MMP9 could potentially yield therapeutic benefits.
... 42 It was additionally reported that ROS constituted an important factor that causes intracellular DNA lesions. 29 γH2AX has served as a biomarker in detecting DNA damage, 43 and in the present study, the accumulation of phosphorylated γH2AX was observed in Fbxl5-KD oocytes ( Figure 4C-E). Excessive ROS generation could cause DNA double-strand break, DNA locus mutation, and other forms of DNA damage. ...
As an E3 ubiquitin ligase, F‐box and leucine‐rich repeat protein 5 (FBXL5) participates in diverse biologic processes. However, the role of Fbxl5 in mouse oocyte meiotic maturation has not yet been fully elucidated. The present study revealed that mouse oocytes depleted of Fbxl5 were unable to complete meiosis, as Fbxl5 silencing led to oocyte meiotic failure with reduced rates of GVBD and polar body extrusion. In addition, Fbxl5 depletion induced aberrant mitochondrial dynamics as we noted the overproduction of reactive oxygen species (ROS) and the accumulation of phosphorylated γH2AX with Fbxl5 knockdown. We also found that Fbxl5‐KD led to the abnormal accumulation of CITED2 proteins in mouse oocytes. Our in vitro ubiquitination assay showed that FBXL5 interacted with CITED2 and that it mediated the degradation of CITED2 protein through the ubiquitination‐proteasome pathway. Collectively, our data revealed critical functions of FBXL5 in redox hemostasis and spindle assembly during mouse oocyte maturation.
... Several groups have revealed that p53 deficiency could protect against acute intestinal inflammation [33,36]. The regulatory effect of MMP9 on p53 has been reported and involves Notch signaling [37,38]. However, the involvement of MMP9-and p53-mediated apoptosis in ulcerative colitis has not been fully explored. ...
... The effects of MMP9 on p53 need to be further clarified. Although MMP9 cannot directly interact with p53 ( Figure S9A), previous studies have shown that MMP9 can regulate intestinal epithelial homeostasis through Notch signaling [37,38,59]. The GSEA scores for Notch signaling positively correlated with MMP9 only in the DSS-treated Olfm4-/-mice and not in the WT mice ( Figure S9B). ...
... We observed a significant effect of Olfm4 on the Mmp9-Notch1-p53 axis in colitis regulation. This axis was proposed in research on colitis-associated cancer [37,38] but has never been assessed in colitis research. ...
Background and Aims: Olfactomedin-4 is a glycoprotein that is upregulated in inflamed gastrointestinal tissues. This study aimed to investigate the role and underlying mechanisms of olfactomedin-4 in ulcerative colitis.
Methods: C57BL/6 mice and olfactomedin-4 knockout mice were fed dextran sulfate sodium in drinking water to establish a colitis model. An in vitro inflammation model was constructed in HCT116 and NCM460 cells stimulated with lipopolysaccharide. The expression of olfactomedin-4 was detected by Western blotting, immunohistochemistry staining, and qRT‒PCR. The differences in the severity of colitis between olfactomedin-4 knockout mice and wild-type mice were compared, and the underlying mechanisms were explored.
Results: Olfactomedin-4 expression was significantly upregulated in colonic tissues of active ulcerative colitis patients and in cellular and mouse models of colitis. Compared with wild-type littermates, olfactomedin-4 knockout mice were more susceptible to dextran sulfate sodium-induced colitis and produced higher levels of proinflammatory cytokines and chemokines. In addition, olfactomedin-4 deficiency significantly promoted intestinal epithelial cell apoptosis and increased intestinal permeability, which was mediated by the p53 pathway. Moreover, olfactomedin-4 directly interacted with and negatively regulated matrix metalloproteinase-9. Inhibiting matrix metalloproteinase-9 significantly decreased colonic p53 expression and ameliorated experimental colitis in olfactomedin-4 knockout mice, while overexpression of matrix metalloproteinase-9 aggravated colitis. Further experiments showed that matrix metalloproteinase-9 regulated p53 through the Notch1 signaling pathway to promote ulcerative colitis progression.
Conclusions: Olfactomedin-4 is significantly upregulated in ulcerative colitis and may protect against colitis by directly inhibiting matrix metalloproteinase-9 and further decreasing p53-mediated apoptosis via Notch1 signaling.
... Neurological deficit scores were determined by the Kruskal-Wallis test. *p < 0.05 vs Sham, # p < 0.05 vs MCAO/R group Matrix metallopeptidases (MMPs) are a family of zinc endopeptidases that can degrade extracellular matrix and basement membrane components [33]. Increased MMP-2 and MMP-9 levels in ischemia/reperfusion correlate with degradation of the integrity of the BBB [17,34]. ...
Blood-brain barrier (BBB) disruption can induce further hemorrhagic transformation in ischemic stroke (IS). miR-671-5p, a micro-RNA, is abundant in the cortex of mammalian brains. Herein, we investigated the roles and potential mechanisms for the effects of miR-671-5p on BBB permeability in IS. Results showed that miR-671-5p levels were significantly downregulated in the cerebral cortex of middle cerebral artery occlusion/reperfusion (MCAO/R) C57/BL6 mice in vivo. miR-671-5p agomir administration via right intracerebroventricular injection significantly reduced infarct volume, improved neurological deficits, the axon of neurons and nerve fiber, attenuated cell injury and apoptosis, as well as reduced BBB permeability in MCAO/R mice. Treatment with miR-671-5p agomir alleviated tight junction proteins degradation, including claudin, occludin, and ZO-1 in MCAO/R mice, and these effects were reversed following NF-κB overexpression. Bend.3 brain endothelial cells were subjected to oxygen and glucose deprivation/reoxygenation (OGD/R) treatment in vivo, and then miR-671-5p agomir was transfected into the cells. This resulted in reduction of cytotoxicity, improved cell viability, trans-endothelial electrical resistance, reduced fluorescein sodium permeability, and inhibited tight junction degradation in Bend.3 OGD/R cells. However, these effects were reversed following NF-κB overexpression. These results demonstrated that upregulation of miR-671-5p in IS models in vivo and in vitro alleviated BBB permeability by targeting NF-κB/MMP-9. In summary, miR-671-5p is a potential therapeutic target for protecting BBB permeability in IS to minimize cerebral hemorrhage transformation.
