Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China.
J Cell Mol Med. 2024 Aug;28(16):e70043. doi: 10.1111/jcmm.70043.
Renal ischaemia-reperfusion injury (RIRI) is a primary cause of acute kidney damage, occurring frequently in situations like renal transplantation, yet the underlying mechanisms were not fully understood. Sentrin-specific protease 1 (SENP1) is an important member of the SENP family, which is widely involved in various diseases. However, the role of SENP1 in RIRI has been unclear. In our study, we discovered that SENP1 was involved in RIRI and reduced renal cell apoptosis and oxidative stress at elevated levels. Further mechanistic studies showed that hypoxia-inducible factor-1α (HIF-1α) was identified as a substrate of SENP1. Furthermore, SENP1 deSUMOylated HIF-1α, which reduced the degradation of HIF-1α, and exerted a renoprotective function. In addition, the protective function was lost after application of the HIF-1α specific inhibitor KC7F2. Briefly, our results fully demonstrated that SENP1 reduced the degradation of HIF-1α and attenuated oxidative stress and apoptosis in RIRI by regulating the deSUMOylation of HIF-1α, suggesting that SENP1 may serve as a potential therapeutic target for the treatment of RIRI.
肾缺血再灌注损伤（RIRI）是急性肾损伤的主要原因，常发生在肾移植等情况下，但其中的机制尚未完全阐明。特异性蛋白酶 1（SENP1）是 SENP 家族的重要成员，广泛参与各种疾病。然而，SENP1 在 RIRI 中的作用尚不清楚。在我们的研究中，我们发现 SENP1 参与了 RIRI，并在高水平时减少了肾细胞凋亡和氧化应激。进一步的机制研究表明，缺氧诱导因子-1α（HIF-1α）是 SENP1 的底物之一。此外，SENP1 去 SUMO 化 HIF-1α，减少了 HIF-1α 的降解，发挥了肾保护作用。此外，应用 HIF-1α 特异性抑制剂 KC7F2 后，这种保护作用丧失。简而言之，我们的结果充分表明，SENP1 通过调节 HIF-1α 的去 SUMO 化，减少了 RIRI 中 HIF-1α 的降解，减轻了氧化应激和细胞凋亡，提示 SENP1 可能成为治疗 RIRI 的潜在治疗靶点。
