NLRP3 inflammasome inhibition attenuates cisplatin-induced renal fibrosis by decreasing oxidative stress and inflammation
| Autor: | Zhaohui Ni, Shan Mou, Zhen Zhang, Xinghua Shao, Ling Wang, Leyi Gu, Yijun Zhou, Chaojun Qi, Haijiao Jin, Shu Li, Jianxiao Shen, Huihua Pang, Qisheng Lin |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Inflammasomes Antineoplastic Agents Inflammation Pharmacology Biology medicine.disease_cause Heterocyclic Compounds 4 or More Rings Mice 03 medical and health sciences 0302 clinical medicine Fibrosis NLR Family Pyrin Domain-Containing 3 Protein medicine Renal fibrosis Animals Humans Sulfones Furans Receptor Retrospective Studies Cisplatin Sulfonamides integumentary system Inflammasome Cell Biology medicine.disease Mice Inbred C57BL Oxidative Stress 030104 developmental biology Indenes 030220 oncology & carcinogenesis Kidney Diseases medicine.symptom Oxidative stress medicine.drug Kidney disease |
| Zdroj: | Experimental Cell Research. 383:111488 |
| ISSN: | 0014-4827 |
| Popis: | Background/Aims The NOD-like receptor, pyrin domain containing-3 (NLRP3) inflammasome is involved in the progression of chronic kidney disease in several rodent models. Here, we investigated whether a specific inhibitor of NLRP3 inflammasome, MCC950, can attenuate cisplatin-induced renal fibrosis. Materials Renal fibrosis was induced via a series of three injections of cisplatin to male C57BL/6 mice (7.5 mg/kg body weight). Activation of NLRP3 inflammasome was detected by immunoblotting, real-time PCR, and immunofluorescence. To validate the protective effect of NLRP3 inflammasome inhibition, MCC950(20 mg/kg body weight) was daily injected into multiple-cisplatin-treated mice intraperitoneally for 14 days, starting from 4 weeks after the first dose of cisplatin. NLRP3-/- mice were used to confirm the role of NLRP3 inflammasome in cisplatin-induced renal fibrosis. Results Mice were euthanized at 6 weeks after the first dose of cisplatin treatment. In multiple-cisplatin-induced murine model, renal fibrosis was accompanied by the activation of NLRP3 inflammasome. MCC950, the specific inhibitor of NLRP3 inflammasome, reduced cisplatin-induced renal dysfunction, tubular damage, interstitial collagen deposit, and the expression of profibrotic parameters. NLRP3 inhibition might protect against cisplatin-induced renal fibrosis through the alleviation of oxidative stress and inflammation. Furthermore, inhibition of NLRP3 inflammasome activation by deleting NLRP3 gene halted the progression of cisplatin-induced renal fibrosis. Conclusion Inhibition of NLRP3 inflammasome attenuates renal fibrosis due to repeated cisplatin injections, and might be identified as a potential target for attenuating cisplatin-induced chronic kidney disease. |
| Databáze: | OpenAIRE |
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