Effects of tumor necrosis factor-α inhibition on kidney fibrosis and inflammation in a mouse model of aristolochic acid nephropathy
| Autor: | Shinya Taguchi, Kengo Azushima, Takahiro Yamaji, Shingo Urate, Toru Suzuki, Eriko Abe, Shohei Tanaka, Shunichiro Tsukamoto, Daisuke Kamimura, Sho Kinguchi, Akio Yamashita, Hiromichi Wakui, Kouichi Tamura |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Science Interleukin-1beta Kidney p38 Mitogen-Activated Protein Kinases Article Etanercept Mice Chronic kidney disease Albuminuria Animals RNA Messenger Renal Insufficiency Chronic Inflammation Pharmacology Multidisciplinary Interleukin-6 Tumor Necrosis Factor-alpha Fibrosis Mice Inbred C57BL Disease Models Animal Aristolochic Acids Medicine Collagen |
| Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-11 (2021) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Tumor necrosis factor (TNF)-α is a potent mediator of inflammation and is involved in the pathophysiology of chronic kidney disease (CKD). However, the effects of TNF-α inhibition on the progression of kidney fibrosis have not been fully elucidated. We examined the effects of TNF-α inhibition by etanercept (ETN) on kidney inflammation and fibrosis in mice with aristolochic acid (AA) nephropathy as a model of kidney fibrosis. C57BL/6 J mice were administered AA for 4 weeks, followed by a 4-week remodeling period. The mice exhibited kidney fibrosis, functional decline, and albuminuria concomitant with increases in renal mRNA expression of inflammation- and fibrosis-related genes. The 8-week ETN treatment partially but significantly attenuated kidney fibrosis and ameliorated albuminuria without affecting kidney function. These findings were accompanied by significant suppression of interleukin (IL)-1β, IL-6, and collagen types I and III mRNA expression. Moreover, ETN tended to reduce the AA-induced increase in interstitial TUNEL-positive cells with a significant reduction in Bax mRNA expression. Renal phosphorylated p38 MAPK was significantly upregulated by AA but was normalized by ETN. These findings indicate a substantial role for the TNF-α pathway in the pathogenesis of kidney fibrosis and suggest that TNF-α inhibition could become an adjunct therapeutic strategy for CKD with fibrosis. |
| Databáze: | OpenAIRE |
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