Bai Yongheng, Wu Cunzao, Hong Weilong, Zhang Xing, Liu Leping, Chen Bicheng
Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Department of Transplantation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Mol Med Rep. 2017 Jul;16(1):737-745. doi: 10.3892/mmr.2017.6628. Epub 2017 May 25.
Sedum sarmentosum Bunge (SSBE) is a perennial plant widely distributed in Asian countries, and its extract is traditionally used for the treatment of certain inflammatory diseases. Our previous studies demonstrated that SSBE has marked renal anti‑fibrotic effects. However, the underlying molecular mechanisms remain to be fully elucidated. The present study identified that SSBE exerts its inhibitory effect on the myofibroblast phenotype and renal fibrosis via the hedgehog signaling pathway in vivo and in vitro. In rats with unilateral ureteral obstruction (UUO), SSBE administration reduced kidney injury and alleviated interstitial fibrosis by decreasing the levels of transforming growth factor (TGF)‑β1 and its receptor, and inhibiting excessive accumulation of extracellular matrix (ECM) components, including type I and III collagens. In addition, SSBE suppressed the expression of proliferating cell nuclear antigen, and this anti‑proliferative activity was associated with downregulation of hedgehog signaling activity in SSBE‑treated UUO kidneys. In cultured renal tubular epithelial cells (RTECs), recombinant TGF‑β1 activated hedgehog signaling, and resulted in induction of the myofibroblast phenotype. SSBE treatment inhibited the activation of hedgehog signaling and partially reversed the fibrotic phenotype in TGF‑β1‑treated RTECs. Similarly, aristolochic acid‑mediated upregulated activity of hedgehog signaling was reduced by SSBE treatment, and thereby led to the abolishment of excessive ECM accumulation. Therefore, these findings suggested that SSBE attenuates the myofibroblast phenotype and renal fibrosis via suppressing the hedgehog signaling pathway, and may facilitate the development of treatments for kidney fibrosis.
垂盆草（Sedum sarmentosum Bunge，SSBE）是一种广泛分布于亚洲国家的多年生植物，其提取物传统上用于治疗某些炎症性疾病。我们之前的研究表明，SSBE具有显著的肾脏抗纤维化作用。然而，其潜在的分子机制仍有待充分阐明。本研究发现，SSBE在体内和体外均通过刺猬信号通路对肌成纤维细胞表型和肾纤维化发挥抑制作用。在单侧输尿管梗阻（UUO）大鼠中，给予SSBE可减轻肾损伤并减轻间质纤维化，其机制为降低转化生长因子（TGF）-β1及其受体水平，并抑制包括I型和III型胶原在内的细胞外基质（ECM）成分的过度积累。此外，SSBE抑制增殖细胞核抗原的表达，这种抗增殖活性与SSBE处理的UUO肾脏中刺猬信号活性的下调有关。在培养的肾小管上皮细胞（RTECs）中，重组TGF-β1激活刺猬信号，并导致肌成纤维细胞表型的诱导。SSBE处理可抑制刺猬信号的激活，并部分逆转TGF-β1处理的RTECs中的纤维化表型。同样，SSBE处理可降低马兜铃酸介导的刺猬信号上调活性，从而消除ECM的过度积累。因此，这些发现表明，SSBE通过抑制刺猬信号通路减轻肌成纤维细胞表型和肾纤维化，并可能有助于肾纤维化治疗方法的开发。
