αKlotho protein has therapeutic activity in contrast-induced acute kidney injury by limiting NLRP3 inflammasome-mediated pyroptosis and promoting autophagy
Autor: | Zhen Zhang, Hong Cai, Zhaohui Ni, Qin Wang, Wenyan Zhou, Jianxiao Shen, Jingkui Wu, Shu Li, Na Jiang, Xinghua Shao, Weiming Zhang, Qisheng Lin, Xuying Zhu |
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Rok vydání: | 2021 |
Předmět: |
Male
0301 basic medicine Mitochondrial ROS Inflammasomes Contrast Media Protective Agents urologic and male genital diseases 03 medical and health sciences 0302 clinical medicine NLR Family Pyrin Domain-Containing 3 Protein Autophagy Pyroptosis medicine Animals Klotho Proteins Protein kinase B PI3K/AKT/mTOR pathway Pharmacology Kidney urogenital system business.industry Acute kidney injury Inflammasome Acute Kidney Injury medicine.disease Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research business medicine.drug |
Zdroj: | Pharmacological Research. 167:105531 |
ISSN: | 1043-6618 |
Popis: | Contrast-induced acute kidney injury (CI-AKI) is a main cause of hospital-acquired renal failure. Nevertheless, limited measures have been shown to be effective for the treatment of CI-AKI. Here, we demonstrated that αKlotho, which is highly expressed in kidney, has therapeutic activity in CI-AKI. Our data showed that αKlotho expression levels were decreased both in the kidney and serum of CI-AKI mice. Administration of αKlotho protein protected the kidney and HK-2 cells against contrast-induced injury. Mechanistically, αKlotho reduced contrast-induced renal tubular cells pyroptosis by limiting NLRP3 inflammasome activation. Meanwhile, αKlotho up-regulated autophagy via inhibiting the AKT/mTOR pathway and decreased mitochondrial ROS level. Inhibition of autophagy blunted the suppression effect of αKlotho on NLRP3 inflammasome activation and cell pyroptosis in contrast-treated HK-2 cells. Taken together, our data suggest that αKlotho protein protects against CI-AKI through inhibiting NLRP3 inflammasome-mediated pyroptosis, which is likely by promoting autophagy. αKlotho may be a promising therapeutic strategy for CI-AKI. |
Databáze: | OpenAIRE |
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