关键词: Piezo 1, 脓毒症相关急性肾损伤, 炎症, 凋亡

Abstract: Ｏｂｊｅｃｔｉｖｅ：To investigate the role and possible mechanism of Piezo 1 in LPS-induced sepsis-associated acute kidney injury (SA-AKI).
Ｍｅｔｈｏｄｏｌｏｇｙ：Establish in vivo and in vitro models of SA-AKI in mice and human proximal renal tubular epithelial cells (HK-2 cells) by LPS, and immunofluorescence and Western blot were used to detect Piezo 1 expression. GsMTx4 was injected into SA-AKI mice, and the renal pathology and renal function were detected. Piezo 1 siRNA or Yoda 1 were used to intervene in LPS-induced HK-2 cells, then the expressions of renal tubular injury markers, inflammatory factors and apoptosis-related marker proteins were detected by Western blot and RT-qPCR, inflammatory factors were detected by ELISA and apoptosis rate was detected by flow cytometry. After treated with Piezo 1 siRNA, the intracellular Ca2+ concentration was detected with a Fluo-4 AM calcium ion fluorescent probe and the expressions of Calpain 2 and Integrin β1 were detected. Integrin β1 expression was detected after PD151746 intervention. After Yoda1 and PD151746 simultaneously intervened in LPS-induced cells, inflammatory factors were detected by ELISA and apoptosis rate was detected by flow cytometry.
Ｒｅｓｕｌｔｓ：Piezo 1 expression was upregulated in the kidneys of mice with SA-AKI and HK-2 cells induced by LPS. GsMTx4 ameliorated renal pathology and renal function damage in SA-AKI mice. Silencing Piezo 1 reduced LPS-induced HK-2 cell damage, inflammation, and apoptosis; however, the above damage was further exacerbated after Yoda 1 intervention. Mechanistically, Piezo 1 knockdown reduced LPS-induced intracellular Ca2+ and the expression of Calpain 2 and Integrin β1. PD151746 reduced the expression of integrin β1 and inhibited inflammation and apoptosis caused by Yoda 1.
Ｃｏｎｃｌｕｓｉｏｎ：Piezo 1 expression is upregulated in renal tubular epithelial cells with SA-AKI, possibly causes inflammation and apoptosis by activating the Ca2+/Calpain 2/Integrin β1 pathway, and which is involved in the progression of SA-AKI.

Key words: Piezo 1, sepsis-associated acute kidney injury, inflammation, apoptosis