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![Roles of Gal-1 in wound microenvironment fibrosis and the roles of Gal-1 and Gal-3 in liver fibrosis were compared (extracellular matrix [ECM], matrix metalloproteinase inhibitor [TIMP], and matrix metalloproteinase [MMP], alpha-smooth muscle actin [α-SMA], chemokine [CCL], chemokine [C-X-C motif] ligand-1 [CXCL1], platelet-derived growth factor [PDGF], vascular endothelial growth factor [VEGF], and transforming growth factor [TGF-β]). Gal-1 induces myofibroblast activation, migration, and proliferation by triggering intracellular reactive oxygen species (ROS) production. Additionally, Gal-1 induces hepatic stellate cell (HSC) activation in myofibroblasts. Gal-3 is an essential protein for TGF-β-mediated myofibroblast activation and matrix production](publication/360723385/figure/fig4/AS:1163067668869120@1654308349009/Roles-of-Gal-1-in-wound-microenvironment-fibrosis-and-the-roles-of-Gal-1-and-Gal-3-in.png)
Roles of Gal-1 in wound microenvironment fibrosis and the roles of Gal-1 and Gal-3 in liver fibrosis were compared (extracellular matrix [ECM], matrix metalloproteinase inhibitor [TIMP], and matrix metalloproteinase [MMP], alpha-smooth muscle actin [α-SMA], chemokine [CCL], chemokine [C-X-C motif] ligand-1 [CXCL1], platelet-derived growth factor [PDGF], vascular endothelial growth factor [VEGF], and transforming growth factor [TGF-β]). Gal-1 induces myofibroblast activation, migration, and proliferation by triggering intracellular reactive oxygen species (ROS) production. Additionally, Gal-1 induces hepatic stellate cell (HSC) activation in myofibroblasts. Gal-3 is an essential protein for TGF-β-mediated myofibroblast activation and matrix production
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Galectins are a family of proteins with at least one carbohydrate-recognition domain. Galectins are present in various tissues and organs and participate in different physiological and pathological molecular reactions in vivo. Wound healing is the basic process of traumatic disease recovery. Wound healing involves three overlapping stages: inflamma...
Citations
... As previously reported, multiple factors can contribute to poor wound healing in diabetes including reduced fibroblast proliferation and migration, and excessive fibroblast apoptosis (Hassanshahi et al. 2019;Yu et al. 2022). The function of fibroblast is to change tissue tension and is primarily responsible for wound healing or tissue contraction in the extracellular matrix of fibrotic organs Roman 2023). ...
Slow wound healing in diabetic patients is a common complication of diabetes. Autologous conditioned serum (ACS) therapy is an emerging and safe biological therapy, and may accelerate the wound healing in diabetes. To investigate the effect of ACS in promoting wound healing in diabetic mice and its possible mechanism. Twenty-four six-week-old male C57BL/6 J mice were selected and divided into 5 groups, including control group (Ctrl), diabetic wound group (DW), ACS treatment group (DW+ACS) and STING pathway validation group (DW+ACS+DMXAA), with six mice in each group. Intervention was initiated after the back incision was performed, and wound healing was assessed on day 0, day 7, and day 14, and wound healing was assessed by hematoxylin and eosin (HE) staining of skin tissue on day 14. At the same time, the wound healing of the fibroblast markers collagen I and α-SMA was measured by immunohistochemistry and western blot. ACS treatment significantly accelerated the diabetic wound according to the wound area and HE staining results. Meanwhile, collagen I and α-SMA concentration evaluated by immunohistochemistry and western blot were remarkably elevated under the ACS interference. The STING signaling pathway was obviously activated in diabetic wound tissues. After the addition of DMXAA, an agonist of STING, the healing function of ACS was dramatically reversed. The application of ACS promotes wound healing in diabetic mice by enhancing fibroblasts. Meanwhile, the STING signaling pathway was inactivated by ACS interference. Hence, ACS can be used in the treatment of wound healing of Diabetes.
... This unique feature allows Gal-4 to serve as a crucial crosslinker and regulator in numerous biological processes 6 . Research highlights its significant roles in stabilizing lipid rafts 8 , facilitating protein apical trafficking 22 , participating in wound healing 23 , influencing intestinal inflammation 24 , and contributing to tumour progression 25 , among other functions. The last decade, Gal-4 has also been implicated in HF 10 and diabetes [11][12][13][14][15] . ...
... There is limited research on whether Gal-4 specifically is involved in fibrosis. However, as indicated in a review by Yu et al., it is believed that galectins have similar and significant roles in the fibrotic process by promoting myofibroblasts to secrete extracellular matrix 23 . This is particularly pertinent, as fibrotic processes are often engaged to replace damaged myocardial tissue in IHD. ...
An association between high Galectin-4 (Gal-4) and prevalence of diabetes in subjects with heart failure (HF) has previously been reported. The purpose of this study was to confirm these findings, as well as to further investigate this association, in a Swedish HF population. In addition, a second aim was to explore Gal-4’s association with obesity and biomarkers of metabolism and heart failure. Gal-4 was measured using a proximity extension array technique in 324 hospitalized HF patients within the Swedish HeArt and bRain failure investigation trial cohort. Obesity was defined as BMI ≥ 30. Multivariable logistic regression models were used to explore associations between Gal-4 and diabetes/obesity, and linear regression models were used to explore the associations between Gal-4 and biomarkers. A total of 309 participants (29.1% female; mean age 74.8 years) provided complete data for the analysis of associations between Gal-4 and diabetes. Additionally, for the analysis of heart failure phenotype, complete data was available for 230 subjects. Gal-4 was positively associated with prevalent diabetes (OR 2.60; CI 95% 1.56–4.32). In multivariable models, Gal-4 levels were significantly associated with obesity, but only for subjects with diabetes (OR 2.48; 1.09–5.62). Additionally, Gal-4 demonstrated a significant association with the incretin Glucose-dependent insulinotropic polypeptide (GIP), as well as with biomarkers of HF. In the stratified analyses, the association between Gal-4 and diabetes was prominent in patients with reduced ejection fraction (n = 160, OR 3.26; 95%CI 1.88–5.66), while it was not observed in those without (n = 70, 1.96 (0.75–5.10)). In this cross-sectional, observational study, higher Gal-4 levels in HF patients were associated with higher GIP levels. Further, increased levels of Gal-4 were associated with increased likelihood of diabetes, and obesity. This association was particularly pronounced in individuals with HF characterized by reduced ejection fraction. Additionally, Gal-4 levels were significantly elevated in heart failure patients with diabetes and obesity.
Introduction:
The rising incidence of liver diseases is a worldwide healthcare concern. However, the therapeutic options to manage chronic inflammation and fibrosis, the processes at the basis of morbidity and mortality of liver diseases, are very limited. Galectin 3 (Gal-3) is a protein implicated in fibrosis in multiple organs. Several Gal-3 inhibitors are currently in clinical development.
Areas covered:
This review describes our current understanding of the role of Gal-3 in chronic liver diseases, with special emphasis on fibrosis. Also, we review therapeutic advances based on Gal-3 inhibition, describing drug properties and their current status in clinical research.
Expert opinion:
Currently, the known effects of Gal-3 point to a direct activation of the NLRP3 inflammasome leading to its activation in liver macrophages and activated macrophages play a key role in tissue fibrogenesis. However, more research is needed to elucidate the role of Gal-3 in the different activation pathways, dissecting the intracellular and extracellular mechanisms of Gal-3, and its role in pathogenesis. Gal-3 could be a target for early therapy of numerous hepatic diseases and, given the lack of therapeutic options for liver fibrosis, there is a strong pharmacologic potential for Gal-3-based therapies.
Lectin, a non-immunogenic origin protein, has properties of binding carbohydrates for the effective wound healing process. The process of wound healing is intricate and encompasses a diverse range of cells, extracellular matrix and soluble mediators involving the hemostasis, coagulation, inflammatory, proliferative, and remodeling or re-epithelialization phases. Lectin has shown to improve the infiltration of neutrophils, stimulate immune cells and regulate mediators like cytokine and growth factors, and promote angiogenesis. It also boosts the fibroblast synthesis, its differentiation into myofibroblast, and collagen deposition leading to complete re-epithelialization. Due to involvement of lectin in all these critical stages of wound healing results in complete wound closure.
This review focuses on the role of lectin in wound healing and its potential application in wound-targeted formulations. It also covers its classification and historical background in a comprehensive manner.
