SMOC2 plays a role in heart failure via regulating TGF-β1/Smad3 pathway-mediated autophagy

Abstract

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.

SMOC2, OGN, FCN3, and SERPINA3 could be biomarkers for the evaluation of acute decompensated heart failure caused by venous congestion

“…SPARC-related modular calcium-binding protein 2 (SMOC2), part of the SPARC family of matricellular proteins, is known to promote endothelial cell proliferation, migration, and angiogenesis 32 . Research indicates that SMOC2 expression escalates in rats experiencing heart failure, and silencing SMOC2 can mitigate heart failure symptoms by modulating autophagy via the TGF-β1/Smad3 signaling pathway 33 . Additionally, mouse studies have demonstrated that SMOC2 knockdown can ameliorate cardiac function impairment and cardiac fibrosis, potentially through the inhibition of the ILK/p38 signaling pathway 34 .…”

“…SPARC-related modular calcium-binding protein 2 (SMOC2), part of the SPARC family of matricellular proteins, is known to promote endothelial cell proliferation, migration, and angiogenesis 32 . Research indicates that SMOC2 expression escalates in rats experiencing heart failure, and silencing SMOC2 can mitigate heart failure symptoms by modulating autophagy via the TGF-β1/Smad3 signaling pathway 33 .…”

Effects of scutellarin on the mechanism of cardiovascular diseases: a review

“…Transforming growth factor (TGF) is a cytokine with numerous functions that regulates and takes part in a variety of biological and pathological events in the heart. Saljic et al (2022) , Gu and Liang, (2023) , Liang et al (2022) , Ren et al (2023) , Alex et al (2023) , Dong et al (2023) . To protect the heart, the TGF-β signaling system controls apoptosis, autophagy, and antifibrotic activities ( Deng et al, 2019 ; Shen et al, 2020a ; Liang et al, 2022 ).…”