Sonic hedgehog (Shh) signaling regulating epithelial–mesenchymal transition (EMT) in cultured rat peritoneal mesothelial cells (PMCs) remains an under‐investigated topic. The current study aimed to elucidate the role of Shh signaling in the regulation of EMT in PMCs to attenuate peritoneal injury, with the view of enhancing the efficacy of peritoneal dialysis (PD). PMCs were initially extracted from male Wistar rats using pancreatic enzyme digestion. The expression of Shh and glioma‐associated oncogene homolog (Gli1) was quantitatively analyzed using the reverse‐transcription quantitative polymerase chain reaction (RT‐qPCR) and western blot analysis. Migration of PMCs was determined using Transwell assay. The expression of Shh, Gli1, and EMT markers including α‐smooth muscle actin (α‐SMA), fibronectin, collagen I, snail1, and E‐cadherin was examined by RT‐qPCR, western blot analysis, and immunofluorescence respectively. High glucose induction was identified to promote cell migration and increase the expression of Shh and Gli1 in a dose‐ and time‐dependent manner in rat PMCs. Cyclopamine (CPN) was observed to block the Shh signaling induced by high glucose, accompanied by cell migration inhibition, decreased expression of α‐SMA, fibronectin, collagen I and snail1 as well as increased expression of E‐cadherin. Altogether, overexpression of Gli1 by transfected Gli1 plasmid promotes cell migration and upregulates α‐SMA, fibronectin, Snail1, and collagen I expression, while downregulating E‐cadherin expression. Shh/Gli1 signaling is important in mediating EMT in rat PMCs, which provides a potential novel therapeutic approach for clinical investigation on renal failure treatment.

中文翻译：

---

腹膜间皮细胞中通过声波刺猬/神经胶质瘤相关癌基因同源物1信号通路调节上皮-间质转化。

音速刺猬（Shh）信号调节培养的大鼠腹膜间皮细胞（PMC）中的上皮-间质转化（EMT）仍是一个研究不足的话题。当前的研究旨在阐明Shh信号在PMCs的EMT调节中减轻腹膜损伤的作用，以增强腹膜透析（PD）的功效。首先使用胰腺酶消化从雄性Wistar大鼠中提取PMC。使用逆转录定量聚合酶链反应（RT-qPCR）和Western印迹分析法定量分析Shh和神经胶质瘤相关癌基因同源物（Gli1）的表达。PMC的迁移使用Transwell分析法确定。Shh，Gli1和EMT标记的表达，包括α-平滑肌肌动蛋白（α-SMA），纤连蛋白，胶原I，snail1，E-cadherin和E-cadherin分别通过RT-qPCR，western blot分析和免疫荧光检查。在大鼠PMC中，高葡萄糖诱导被发现促进细胞迁移并以剂量和时间依赖性方式增加Shh和Gli1的表达。观察到环巴胺（CPN）可以阻断高糖诱导的Shh信号传导，并伴随细胞迁移抑制，α-SMA，纤连蛋白，胶原蛋白I和snail1的表达降低以及E-钙粘蛋白的表达增加。总之，通过转染的Gli1质粒过度表达Gli1可以促进细胞迁移并上调α-SMA，纤连蛋白，Snail1和胶原I的表达，同时下调E-钙黏着蛋白的表达。Shh / Gli1信号传导在介导大鼠PMC中的EMT中很重要，