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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MDPI AG
2021-11-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/11/3057 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T05:36:30Z |
| format | Article |
| id | doaj.art-956a7271639a4c33a89b11514efe8814 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T05:36:30Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-956a7271639a4c33a89b11514efe88142023-11-22T22:50:40ZengMDPI AGCells2073-44092021-11-011011305710.3390/cells10113057STAT6 Deficiency Attenuates Myeloid Fibroblast Activation and Macrophage Polarization in Experimental Folic Acid NephropathyBaihai Jiao0Changlong An1Hao Du2Melanie Tran3Penghua Wang4Dong Zhou5Yanlin Wang6Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT 06030, USADivision of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT 06030, USADivision of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT 06030, USADivision of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT 06030, USADepartment of Immunology, University of Connecticut School of Medicine, Farmington, CT 06030, USADivision of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT 06030, USADivision of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT 06030, USARenal 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.https://www.mdpi.com/2073-4409/10/11/3057STAT6macrophage polarizationfibroblastsfibrosischronic kidney disease |
| spellingShingle | 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 Cells STAT6 macrophage polarization fibroblasts fibrosis chronic kidney disease |
| title | 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_short | 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 |
| topic | STAT6 macrophage polarization fibroblasts fibrosis chronic kidney disease |
| url | https://www.mdpi.com/2073-4409/10/11/3057 |
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