Ren Yu, Wu Yun, He Wenshuai, Tian Yingjie, Zhao Xingsheng
Scientific Research Department, Inner Mongolia People's Hospital, Inner Mongolia Autonomous Region, Hohhot, 010017, China.
Cardiology Department, Inner Mongolia People's Hospital, Inner Mongolia Autonomous Region, Hohhot, 010017, China.
Open Med (Wars). 2023 Jul 11;18(1):20230752. doi: 10.1515/med-2023-0752. eCollection 2023.
Heart failure (HF) is a major global cause of morbidity and mortality. This study aimed to elucidate the role of secreted protein acidic and rich in cysteine-related modular calcium-binding protein 2 (SMOC2) in HF development and its underlying mechanism. Using a rat HF model, SMOC2 expression was examined and then knocked down via transfection to assess its impact on cardiac function and damage. The study also evaluated the effects of SMOC2 knockdown on autophagy-related molecules and the transforming growth factor beta 1 (TGF-β1)/SMAD family member 3 (Smad3) signaling pathway. Intraperitoneal injection of the TGF-β agonist (SRI-011381) into the HF rat model was performed to explore the SMOC2-TGF-β1/Smad3 pathway relationship. SMOC2 expression was elevated in HF rats, while its downregulation improved cardiac function and damage. SMOC2 knockdown reversed alterations in the LC3-II/I ratio, Beclin-1, and p62 levels in HF rats. Through transmission electron microscope, we observed that SMOC2 knockdown restored autophagosome levels. Furthermore, SMOC2 downregulation inhibited the TGF-β1/Smad3 signaling pathway, which was counteracted by SRI-011381. In conclusion, SMOC2 knockdown inhibits HF development by modulating TGF-β1/Smad3 signaling-mediated autophagy, suggesting its potential as a therapeutic target for HF.
心力衰竭（HF）是全球发病和死亡的主要原因。本研究旨在阐明富含半胱氨酸的酸性分泌蛋白相关模块化钙结合蛋白2（SMOC2）在HF发生发展中的作用及其潜在机制。利用大鼠HF模型，检测SMOC2表达，然后通过转染将其敲低，以评估其对心脏功能和损伤的影响。该研究还评估了敲低SMOC2对自噬相关分子以及转化生长因子β1（TGF-β1）/SMAD家族成员3（Smad3）信号通路的影响。对HF大鼠模型进行腹腔注射TGF-β激动剂（SRI-011381），以探究SMOC2-TGF-β1/Smad3通路的关系。HF大鼠中SMOC2表达升高，而其下调改善了心脏功能和损伤。敲低SMOC2可逆转HF大鼠中LC3-II/I比值、Beclin-1和p62水平的改变。通过透射电子显微镜，我们观察到敲低SMOC2可恢复自噬体水平。此外，下调SMOC2可抑制TGF-β1/Smad3信号通路，而SRI-011381可抵消这种抑制作用。总之，敲低SMOC2通过调节TGF-β1/Smad3信号介导的自噬来抑制HF的发展，表明其作为HF治疗靶点的潜力。
