Inhibition of class I HDACs attenuates renal interstitial fibrosis in a murine model
| Autor: | Min Yang, Sheng Chang, Zhonghua Klaus Chen, Xue Zhang, Yuliang Guo, Li Tian, Yan Yu, Gen Chen |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Apoptosis SMAD Kidney urologic and male genital diseases Histone Deacetylases Cell Line Transforming Growth Factor beta1 Extracellular matrix 03 medical and health sciences Histone H3 0302 clinical medicine Depsipeptides medicine Renal fibrosis Animals Renal Insufficiency Chronic Fibroblast Cell Proliferation Pharmacology Chemistry Epithelial Cells Fibroblasts medicine.disease Fibrosis Extracellular Matrix Rats Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research Signal transduction Mothers against decapentaplegic Ureteral Obstruction Kidney disease |
| Zdroj: | Pharmacological Research. 142:192-204 |
| ISSN: | 1043-6618 |
| DOI: | 10.1016/j.phrs.2019.02.011 |
| Popis: | Renal interstitial fibrosis is the most common of all the forms of chronic kidney disease (CKD). Research has shown that histone deacetylases (HDACs) participate in the process leading to renal fibrosis. However, the effects of class I HDAC inhibitors on the mechanisms of onset and progression of renal interstitial fibrosis are still unclear. Here, we present the effects and mechanisms of action of FK228 (a selective inhibitor of class I HDACs) in the murine model of unilateral ureteral obstruction (UUO) and in vitro models. We investigated the antifibrotic role of FK228 in a murine model of UUO. We used two key effector cell populations, rat renal interstitial fibroblasts and renal tubular epithelial cells exposed to recombinant transforming growth factor-beta 1 (TGF-β1), to explore the mechanistic pathways among in vitro models. The results indicated that FK228 significantly suppressed the production of extracellular matrix (ECM) in both in vivo and in vitro models. FK228 inhibited renal fibroblast activation and proliferation and increased the acetylation of histone H3. We found that FK228 also inhibited the small mothers against decapentaplegic (Smad) and non-Smad signaling pathways. So FK228 could significantly suppress renal interstitial fibrosis via Smad and non-Smad pathways. FK228 may be the basis for a new and effective medicine for alleviating renal fibrosis in the future. |
| Databáze: | OpenAIRE |
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