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Dapagliflozin alleviates cardiac fibrosis through suppressing EndMT and fibroblast activation via AMPK α/TGF-β/Smad signalling in type 2 diabetic rats
This study aimed to evaluate the effect of SGLT2 inhibitor dapagliflozin (DAPA) on DCM especially for cardiac fibrosis and explore the underlying mechanism. In vivo, the model of type 2 diabetic rats was built with high-fat feeding and streptozotocin injection. Untreated diabetic rats showed cardiac dysfunction, increased myocardial fibrosis and EndMT, which was attenuated after treatment with DAPA and metformin. In vitro, HUVECs and primary cardiac fibroblasts were treated with DAPA and exposed to high glucose (HG). HG-induced EndMT in HUVECs and collagen secretion of fibroblasts were markedly inhibited by DAPA. Up-regula...
Source: J Cell Mol Med - June 25, 2021 Category: Molecular Biology Authors: Jingjing Tian Mingjun Zhang Mengying Suo Dian Liu Xuyang Wang Ming Liu Jinyu Pan Tao Jin Fengshuang An Source Type: research

Mesenchymal stromal cells protect hepatocytes from lipotoxicity through alleviation of endoplasmic reticulum stress by restoring SERCA activity.
Abstract The aim of this study was to investigate how mesenchymal stromal cells (MSCs) modulate metabolic balance and attenuate hepatic lipotoxicity in the context of non-alcoholic fatty liver disease (NAFLD). In vivo, male SD rats were fed with high-fat diet (HFD) to develop NAFLD; then, they were treated twice by intravenous injections of rat bone marrow MSCs. In vitro, HepG2 cells were cocultured with MSCs by transwell and exposed to palmitic acid (PA) for 24 hours. The endoplasmic reticulum (ER) stressor thapsigargin and sarco/ER Ca2+ -ATPase (SERCA2)-specific siRNA were used to explore the regulation of ER s...
Source: J Cell Mol Med - February 16, 2021 Category: Molecular Biology Authors: Li L, Zeng X, Liu Z, Chen X, Li L, Luo R, Liu X, Zhang J, Liu J, Lu Y, Cheng J, Chen Y Tags: J Cell Mol Med Source Type: research

FGF21 induces autophagy-mediated cholesterol efflux to inhibit atherogenesis via RACK1 up-regulation.
In this study, ApoE-/- mice were fed a high-fat diet (HFD) with or without FGF21 and FGF21 + 3-Methyladenine (3MA) for 12 weeks. Our results showed that FGF21 inhibited AS in HFD-fed ApoE-/- mice, which was reversed by 3MA treatment. Moreover, FGF21 increased plaque RACK1 and autophagy-related protein (LC3 and beclin-1) expression in ApoE-/- mice, thus preventing AS. However, these proteins were inhibited by LV-RACK1 shRNA injection. Foam cell development is a crucial determinant of AS, and cholesterol efflux from foam cells represents an important defensive measure of AS. In this study, foam cells were treated with FGF...
Source: J Cell Mol Med - March 29, 2020 Category: Molecular Biology Authors: Xiaolong L, Dongmin G, Liu M, Zuo W, Huijun H, Qiufen T, XueMei H, Wensheng L, Yuping P, Jun L, Zhaolin Z Tags: J Cell Mol Med Source Type: research