Capsaicin ameliorates renal fibrosis by inhibiting TGF-β1-Smad2/3 signaling
Capsaicin ameliorates renal fibrosis by inhibiting TGF-β1-Smad2/3 signaling
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DOI：
10.1016/j.phymed.2022.154067
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发表时间：
2022-03-26
期刊：
影响因子：
7.9
通讯作者：
Zhang, Jingbo
中科院分区：
文献类型：
--
作者：
Liu, Zhenyu;Wang, Weili;Zhang, Jingbo
背景和目的：慢性肾脏病（CKD）是一种全球性的难治性疾病，其特点是肾纤维化，目前尚无有效的治疗策略。辣椒素具有多种药理作用，包括肝纤维化和心脏纤维化。然而，辣椒素是否在肾纤维化中发挥治疗作用仍不清楚。方法：我们研究了辣椒素在两种小鼠肾纤维化模型中的抗纤维化作用，如下：C57 BL/6 J小鼠进行单侧输尿管梗阻（UUO），并喂以富含腺嘌呤的饮食。我们发现并验证了辣椒素在人近端肾小管上皮细胞（HK 2）中的作用机制。我们主要采用组织化学，免疫组织化学和免疫荧光染色，蛋白质印迹分析，生化检查和其他工具来研究辣椒素对肾纤维化的影响和潜在的mechanism.Results：辣椒素治疗显着减轻纤维连接蛋白和胶原蛋白沉积在肾小管上皮细胞损伤的肾脏UUO和腺嘌呤喂养的小鼠。同时，辣椒素处理明显降低了α-SMA的表达。此外，辣椒素治疗显着保护肾小管上皮细胞的表型改变，通过增加E-钙粘蛋白的表达和减少波形蛋白的表达在肾纤维化。结论：辣椒素可抑制肾小管上皮细胞TGF-β 1-Smad 2/3信号通路，抑制肾小管上皮细胞表型改变，抑制肌成纤维细胞活化，减轻肾小管上皮细胞表型改变，从而减轻肾纤维化。因此，我们的研究结果可能会提供一个新的见解辣椒素在肾纤维化的临床应用。
Background and purpose: Chronic kidney disease (CKD), characterized by renal fibrosis, is a global refractory disease with few effective therapeutic strategies. It has been reported that capsaicin exerts many pharmacological effects including liver and cardiac fibrosis. However, whether capsaicin plays a therapeutic role in renal fibrosis remains unclear.Methods: We investigated antifibrotic effects of capsaicin in two mouse renal fibrosis models as follows: C57BL/6J mice were subjected to unilateral ureteral obstruction (UUO) and fed with an adenine-rich diet. We uncovered and verified the mechanisms of capsaicin in human proximal tubular epithelial cells (HK2). We mainly used histochemistry, immunohistochemistry and immunofluorescence staining, western blot assay, biochemical examination and other tools to examine the effects of capsaicin on renal fibrosis and the underlying mechanisms.Results: Capsaicin treatment significantly alleviated fibronectin and collagen depositions in the tubulointerstitium of the injured kidneys from UUO and adenine-fed mice. Meanwhile, capsaicin treatment obviously reduced alpha-SMA expression. Moreover, capsaicin treatment dramatically protected against the phenotypic alteration of tubular epithelial cells by increasing E-cadherin expression and decreasing vimentin expression during renal fibrosis. Mechanistically, capsaicin treatment effectively suppressed alpha-SMA and vimentin expressions but promoted E-cadherin expression in HK2 cells mainly through the inhibition of TGF-beta 1-Smad2/3 signaling.Conclusion: Capsaicin significantly ameliorated renal fibrosis possibly by retarding the activation of myofibroblasts and protecting against the phenotypic alteration of tubular epithelial cells mainly through the inhibition of TGF-beta 1-Smad2/3 signaling. Thus, our findings may provide a new insight into the clinical application of capsaicin in renal fibrosis.