Department of General Practice, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China.
Department of Radiology, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China.
Mol Med Rep. 2020 Aug;22(2):1035-1043. doi: 10.3892/mmr.2020.11178. Epub 2020 May 22.
Klotho is a type of single‑pass transmembrane protein that is important for the proper function of numerous organs. The aim of the present study was to investigate the role of Klotho in sepsis‑associated myocardial damage. In the present study, reverse transcription‑quantitative PCR, western blotting and ELISA were conducted to examine the expression levels of function genes, and flow cytometry was performed to detect cell apoptosis and reactive oxygen species. The present study demonstrated that Klotho expression was significantly downregulated in septic mice and that the myocardial function of septic mice improved after treatment with exogenous Klotho protein. It further demonstrated that indoxyl sulfate inhibited the expression of Klotho protein. In addition, decreased Klotho protein further led to activation of the reactive oxygen species‑p38 mitogen‑activated protein kinase signaling pathway, finally resulting in myocardial damage. In conclusion, Klotho protein may be a key regulator in the myocardial damage of cardiorenal syndrome in sepsis. It also has a potential to be a therapeutic target for sepsis‑associated myocardial damage in the future.
Klotho 是一种单次跨膜蛋白，对许多器官的正常功能非常重要。本研究旨在探讨 Klotho 在脓毒症相关心肌损伤中的作用。在本研究中，采用逆转录-定量 PCR、western blot 和 ELISA 检测功能基因的表达水平，采用流式细胞术检测细胞凋亡和活性氧。本研究表明，Klotho 在脓毒症小鼠中的表达显著下调，外源性 Klotho 蛋白治疗后脓毒症小鼠的心肌功能得到改善。进一步表明，硫酸吲哚酚抑制 Klotho 蛋白的表达。此外，Klotho 蛋白的减少进一步导致活性氧-p38 丝裂原激活蛋白激酶信号通路的激活，最终导致心肌损伤。综上所述，Klotho 蛋白可能是脓毒症心肾综合征心肌损伤的关键调节因子。它也有可能成为未来脓毒症相关心肌损伤的治疗靶点。
