Shenqi Wan inhibits cellular senescence to alleviate renal fibrosis by modulating the AQP1/TGF-β1/ITPR1 axis

Renal fibrosis is a common terminal pathway for various CKDs. Shenqi Wan (SQW) can reduce the development of renal fibrosis and may be associated with aquaporin 1 (AQP1) as discovered previously.

The mechanism of SQW in mitigating the progression of renal fibrosis and alleviating CKD was analyzed.

UPLC-Q-TOF-MS was used to identify the components of SQW. Clinical samples were used to validate AQP1 expression. Adenine-induced and AQP1^-/- mice were used for in vivo experiments, whereas AQP1-knockdown HK-2 cells were used for in vitro experiments. Transcriptomic sequencing was used to analyze the molecular alterations of AQP1 and its associated biomarkers and to determine changes in renal tissues and cells.

SQW significantly decreased elevated total urine protein and serum creatinine levels in wild-type mice with CKD and alleviated kidney damage and fibrosis. Renal dysfunction and cellular senescence were significantly exacerbated in AQP1 knockout mice. SQW increased AQP1 expression and exerted a protective effect in adenine-induced CKD in wide-type mice. Furthermore, AQP1 expression was decreased markedly in kidney biopsies of patients with CKD compared to healthy subjects. AQP1 mediated the activation of TGF-β1, which was significantly elevated in kidney tissues in CKD. SQW administration did not significantly alleviate renal dysfunction and cellular senescence in adenine-induced AQP1^-/- mice in vivo and AQP1-knockdown human renal proximal tubular HK-2 cells in vitro, indicating AQP1 as a key target for SQW in alleviating CKD.

SQW alleviated cellular senescence and mitochondrial dysfunction by upregulating AQP1 and targeting the AQP1/TGF-β1/ITPR1 axis, thereby mitigating CKD.