Int J Stem Cells.  2021 Aug;14(3):320-330. 10.15283/ijsc20186.

Galectin-3 Derived from HucMSC Exosomes Promoted Myocardial Fibroblast-to-Myofibroblast Differentiation Associated with β-catenin Upregulation

Affiliations
  • 1School of Medicine, Jiangsu University, Zhenjiang, China
  • 2Department of Obstetrics, Affiliated Hospital of Jiangsu University, Zhenjiang, China
  • 3Department of Clinical Laboratory, Zhenjiang Provincial Blood Center, Zhenjiang, China

Abstract

Background and Objectives
Galectin-3 promotes fibroblast-to-myofibroblast differentiation and facilitates injury repair. Previous studies have shown that exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-ex) promote the differentiation of myocardial fibroblasts into myofibroblasts under inflammatory environment. Whether hucMSC-ex derived Galectin-3 (hucMSC-ex-Galectin-3) plays an important role in fibroblast-to-myofibroblast differentiation is the focus of this study.
Methods and Results
Galectin-3 was knocked-down by siRNA in hucMSCs, and then exosomes were extracted. Fibroblasts were treated with LPS, LPS+hucMSC-ex, LPS+negative control-siRNA-ex (NC-ex), or LPS+ Galectin-3-siRNA-ex (si-ex) in vitro. The coronary artery of the left anterior descending (LAD) branch was permanently ligated, followed by intramyocardial injection with phosphate buffered saline(PBS), hucMSC-ex, hucMSC-NC-ex, or hucMSC-si-ex in vivo. Western blot, RT-PCR, and immunohistochemistry were used to detect the expression of markers related to fibroblast-to-myofibroblast differentiation and inflammatory factors. Migration and contraction functions of fibroblasts were evaluated using Transwell migration and collagen contraction assays, respectively. β-catenin expression was detected by western blot and immunofluorescence. The results showed that hucMSC-ex increased the protein expression of myofibroblast markers, anti-inflammatory factors, and β-catenin. HucMSC-ex also reduced the migration and promoted the contractility of fibroblasts. However, hucMSC-si-ex did not show these activities.
Conclusions
HucMSC-ex-Galectin-3 promoted the differentiation of cardiac fibroblasts into myofibroblasts in an inflammatory environment, which was associated with increased β-catenin levels.

Keyword

Mesenchymal stem cell; Galectin-3; Cardiac fibroblasts; Myofibroblasts
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