STAT6 Deficiency Attenuates Myeloid Fibroblast Activation and Macrophage Polarization in Experimental Folic Acid Nephropathy

Renal fibrosis is a pathologic feature of chronic kidney disease, which can lead to end-stage kidney disease. Myeloid fibroblasts play a central role in the pathogenesis of renal fibrosis. However, the molecular mechanisms pertaining to myeloid fibroblast activation remain to be elucidated. In the p...

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Autores principales:	Baihai Jiao, Changlong An, Hao Du, Melanie Tran, Penghua Wang, Dong Zhou, Yanlin Wang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	STAT6 macrophage polarization fibroblasts fibrosis chronic kidney disease Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/956a7271639a4c33a89b11514efe8814
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spelling	oai:doaj.org-article:956a7271639a4c33a89b11514efe88142021-11-25T17:10:56ZSTAT6 Deficiency Attenuates Myeloid Fibroblast Activation and Macrophage Polarization in Experimental Folic Acid Nephropathy10.3390/cells101130572073-4409https://doaj.org/article/956a7271639a4c33a89b11514efe88142021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3057https://doaj.org/toc/2073-4409Renal fibrosis is a pathologic feature of chronic kidney disease, which can lead to end-stage kidney disease. Myeloid fibroblasts play a central role in the pathogenesis of renal fibrosis. However, the molecular mechanisms pertaining to myeloid fibroblast activation remain to be elucidated. In the present study, we examine the role of signal transducer and activator of transcription 6 (STAT6) in myeloid fibroblast activation, macrophage polarization, and renal fibrosis development in a mouse model of folic acid nephropathy. STAT6 is activated in the kidney with folic acid nephropathy. Compared with folic-acid-treated wild-type mice, STAT6 knockout mice had markedly reduced myeloid fibroblasts and myofibroblasts in the kidney with folic acid nephropathy. Furthermore, STAT6 knockout mice exhibited significantly less CD206 and PDGFR-β dual-positive fibroblast accumulation and M2 macrophage polarization in the kidney with folic acid nephropathy. Consistent with these findings, STAT6 knockout mice produced less extracellular matrix protein, exhibited less severe interstitial fibrosis, and preserved kidney function in folic acid nephropathy. Taken together, these results have shown that STAT6 plays a critical role in myeloid fibroblasts activation, M2 macrophage polarization, extracellular matrix protein production, and renal fibrosis development in folic acid nephropathy. Therefore, targeting STAT6 may provide a novel therapeutic strategy for fibrotic kidney disease.Baihai JiaoChanglong AnHao DuMelanie TranPenghua WangDong ZhouYanlin WangMDPI AGarticleSTAT6macrophage polarizationfibroblastsfibrosischronic kidney diseaseBiology (General)QH301-705.5ENCells, Vol 10, Iss 3057, p 3057 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	STAT6 macrophage polarization fibroblasts fibrosis chronic kidney disease Biology (General) QH301-705.5
spellingShingle	STAT6 macrophage polarization fibroblasts fibrosis chronic kidney disease Biology (General) QH301-705.5 Baihai Jiao Changlong An Hao Du Melanie Tran Penghua Wang Dong Zhou Yanlin Wang STAT6 Deficiency Attenuates Myeloid Fibroblast Activation and Macrophage Polarization in Experimental Folic Acid Nephropathy
description	Renal fibrosis is a pathologic feature of chronic kidney disease, which can lead to end-stage kidney disease. Myeloid fibroblasts play a central role in the pathogenesis of renal fibrosis. However, the molecular mechanisms pertaining to myeloid fibroblast activation remain to be elucidated. In the present study, we examine the role of signal transducer and activator of transcription 6 (STAT6) in myeloid fibroblast activation, macrophage polarization, and renal fibrosis development in a mouse model of folic acid nephropathy. STAT6 is activated in the kidney with folic acid nephropathy. Compared with folic-acid-treated wild-type mice, STAT6 knockout mice had markedly reduced myeloid fibroblasts and myofibroblasts in the kidney with folic acid nephropathy. Furthermore, STAT6 knockout mice exhibited significantly less CD206 and PDGFR-β dual-positive fibroblast accumulation and M2 macrophage polarization in the kidney with folic acid nephropathy. Consistent with these findings, STAT6 knockout mice produced less extracellular matrix protein, exhibited less severe interstitial fibrosis, and preserved kidney function in folic acid nephropathy. Taken together, these results have shown that STAT6 plays a critical role in myeloid fibroblasts activation, M2 macrophage polarization, extracellular matrix protein production, and renal fibrosis development in folic acid nephropathy. Therefore, targeting STAT6 may provide a novel therapeutic strategy for fibrotic kidney disease.
format	article
author	Baihai Jiao Changlong An Hao Du Melanie Tran Penghua Wang Dong Zhou Yanlin Wang
author_facet	Baihai Jiao Changlong An Hao Du Melanie Tran Penghua Wang Dong Zhou Yanlin Wang
author_sort	Baihai Jiao
title	STAT6 Deficiency Attenuates Myeloid Fibroblast Activation and Macrophage Polarization in Experimental Folic Acid Nephropathy
title_short	STAT6 Deficiency Attenuates Myeloid Fibroblast Activation and Macrophage Polarization in Experimental Folic Acid Nephropathy
title_full	STAT6 Deficiency Attenuates Myeloid Fibroblast Activation and Macrophage Polarization in Experimental Folic Acid Nephropathy
title_fullStr	STAT6 Deficiency Attenuates Myeloid Fibroblast Activation and Macrophage Polarization in Experimental Folic Acid Nephropathy
title_full_unstemmed	STAT6 Deficiency Attenuates Myeloid Fibroblast Activation and Macrophage Polarization in Experimental Folic Acid Nephropathy
title_sort	stat6 deficiency attenuates myeloid fibroblast activation and macrophage polarization in experimental folic acid nephropathy
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/956a7271639a4c33a89b11514efe8814
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_version_	1718412666072989696

STAT6 Deficiency Attenuates Myeloid Fibroblast Activation and Macrophage Polarization in Experimental Folic Acid Nephropathy

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