Department of Urology, First Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, China.
Urolithiasis. 2022 Feb;50(1):11-20. doi: 10.1007/s00240-021-01292-0. Epub 2021 Dec 3.
The mechanism underlying phosphatidylserine eversion in renal tubule cells following calcium oxalate-mediated damage remains unclear; therefore, we investigated the effects of TGF-β1/Smad signaling on phosphatidylserine eversion in the renal tubule cell membrane during the early stage of kidney stone development. In a rat model of early stage of calcium oxalate stone formation, phosphatidylserine eversion on the renal tubular cell membrane was detected by flow cytometry, and the expression of TGF-β1 (transforming growth factor-β1), Smad7, and phospholipid scramblase in the renal tubular cell membrane was measured by western blotting. We observed that the TGF-β1/Smad signaling pathway increased phosphatidylserine eversion at the organism level. The results of in vitro studies demonstrated that oxalate exposure to renal tubule cells induced TGF-β1 expression, increasing phospholipid scramblase activity and phosphatidylserine eversion in the renal tubule cell membrane. These results indicate that TGF-β1 stimulates phosphatidylserine eversion by increasing the phospholipid scramblase activity in the renal tubule cell membrane during the early stage of kidney stone development. The results of this study form a basis for further detailed research on the development of therapeutic agents that specifically treat urolithiasis and exert fewer adverse effects.
草酸钙介导损伤后肾小管细胞中磷脂酰丝氨酸外翻的机制尚不清楚；因此，我们研究了 TGF-β1/Smad 信号通路在肾结石形成早期对肾小管细胞膜磷脂酰丝氨酸外翻的影响。在草酸钙结石形成早期大鼠模型中，通过流式细胞术检测肾小管细胞膜上的磷脂酰丝氨酸外翻，通过 Western blot 检测肾小管细胞膜中 TGF-β1（转化生长因子-β1）、Smad7 和磷脂翻转酶的表达。我们观察到 TGF-β1/Smad 信号通路在机体水平上增加了磷脂酰丝氨酸外翻。体外研究结果表明，草酸暴露于肾小管细胞中诱导 TGF-β1 的表达，增加了肾小管细胞膜中磷脂翻转酶的活性和磷脂酰丝氨酸外翻。这些结果表明，TGF-β1 通过增加肾结石形成早期肾小管细胞膜中的磷脂翻转酶活性来刺激磷脂酰丝氨酸外翻。本研究结果为进一步研究专门治疗尿石症且不良反应较少的治疗药物的开发奠定了基础。
