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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

FKN Facilitates HK-2 Cell EMT and Tubulointerstitial Lesions via the Wnt/ β-Catenin Pathway in a Murine Model of Lupus Nephritis
In this study, we therefore examined whether FKN could stimulate the process of EMT, NF-kB, TGFβ, CCL22, F4/80, inflammation, and tubulointerstitial fibrosis in a murine model of LN. We also determined whether FKN was involved in the EMT process of Wnt/β-catenin-expressing HK-2 cells. Mechanistically, we ascertained, for the first time, whether FKN up-regulated EMT-related gene signatures (e.g., vimentin, α-SMA), and hence, renal tubulointerstitial fibrogenesis, and the role of the Wnt/β-catenin signaling pathway in this process. Materials and Methods Cell Culture, Stable Infection, and Gr...
Source: Frontiers in Immunology - April 29, 2019 Category: Allergy & Immunology Source Type: research

Cardiotonic steroid ouabain stimulates steroidogenesis in Leydig cells via the α3 isoform of the sodium pump
Publication date: Available online 28 April 2019Source: The Journal of Steroid Biochemistry and Molecular BiologyAuthor(s): Neha Upmanyu, Raimund Dietze, Ahmed Bulldan, Georgios Scheiner-BobisAbstractCardiotonic steroids such as ouabain are potent inhibitors of the sodium pump and have been widely used for centuries in the treatment of congestive heart failure. In recent decades, however, they have also been identified as hormone-like molecules that trigger signaling cascades of physiological relevance by using the various sodium pump α subunit isoforms as receptors. The murine Leydig cell line MLTC-1 expresses both the u...
Source: The Journal of Steroid Biochemistry and Molecular Biology - April 29, 2019 Category: Biochemistry Source Type: research