C1q/tumor necrosis factor-related protein-6 suppresses the angiotensin II-induced differentiation of cardiac fibroblasts to myofibroblasts via activation of the AMPK pathway

IF 2.7 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2024-11-17 DOI:10.1016/j.tice.2024.102627

Dan Wu, Shuyu Li, Meng Chen, Shujing Zhang, Qian Wang

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引用次数: 0

Abstract

C1q/tumor necrosis factor-related protein-6 (CTRP6) has multiple protective effects against cardiovascular diseases. Myofibroblast differentiation plays a critical role in cardiac fibrosis under various cardiac pathological conditions. The aim of the present study was to determine the effects of CTRP6 on cardiac fibrosis, and to identify the possible mechanisms of action. Toward this end, we measured the expression of fibrotic markers, including collagen I, collagen III, CTGF, and TGFβ1, and assessed the effects of CTRP6 on cardiac fibroblast differentiation into myofibroblasts. CTRP6 inhibited the expression of the angiotensin II (Ang II)-induced myofibroblast markers α-SMA and SM22, and of profibrotic molecules, including collagen I, collagen III, CTGF, TGFβ1, MMP2, MMP9, and TIMP1. Furthermore, CTRP6 significantly attenuated the proliferation and migration of cardiac fibroblasts incubated with Ang II and activated the phosphorylation of AMP-activated protein kinase (AMPK). Incubation with an AMPK inhibitor reversed the subsequent inhibitory effects of CTRP6 on Ang II-induced myofibroblast differentiation. Therefore, CTRP6 suppresses cardiac fibrosis by inhibition of myofibroblast differentiation via AMPK pathway activation, suggesting CTRP6 as a target for the treatment of cardiac fibrosis.

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C1q/肿瘤坏死因子相关蛋白-6通过激活AMPK途径抑制血管紧张素II诱导的心脏成纤维细胞向肌成纤维细胞分化。

C1q/肿瘤坏死因子相关蛋白-6（CTRP6）对心血管疾病具有多种保护作用。在各种心脏病理条件下，肌成纤维细胞分化在心脏纤维化中起着关键作用。本研究旨在确定 CTRP6 对心脏纤维化的影响，并找出可能的作用机制。为此，我们测量了纤维化标志物的表达，包括胶原 I、胶原 III、CTGF 和 TGFβ1，并评估了 CTRP6 对心脏成纤维细胞分化为肌成纤维细胞的影响。CTRP6抑制了血管紧张素II（Ang II）诱导的肌成纤维细胞标记物α-SMA和SM22的表达，以及包括胶原蛋白I、胶原蛋白III、CTGF、TGFβ1、MMP2、MMP9和TIMP1在内的促纤维化分子的表达。此外，CTRP6 还能明显减少与 Ang II 培养的心脏成纤维细胞的增殖和迁移，并激活 AMP 激活蛋白激酶（AMPK）的磷酸化。用 AMPK 抑制剂孵育可逆转 CTRP6 随后对 Ang II 诱导的肌成纤维细胞分化的抑制作用。因此，CTRP6通过激活AMPK通路抑制肌成纤维细胞分化，从而抑制心脏纤维化，这表明CTRP6是治疗心脏纤维化的一个靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.