Stromal vascular fraction inhibits renal fibrosis by regulating metabolism and inflammation in obstructive nephropathy
Obstructive nephropathy is one of the leading causes of kidney injury and fibrosis, which can lead to end-stage renal disease (ESRD). Stromal vascular fraction (SVF), a heterogeneous cell mixture derived from adipose tissue, has been widely used for regenerative medicine across many preclinical mode...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1559446/full |
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| author | Guang Yue Guang Yue Yunjie Yang Hongshuai Jia Hongshuai Jia Yangyang Wu Yangyang Wu Lifei Ma Xiaoyu Yi Yuandong Tao Huixia Zhou Huixia Zhou |
| author_facet | Guang Yue Guang Yue Yunjie Yang Hongshuai Jia Hongshuai Jia Yangyang Wu Yangyang Wu Lifei Ma Xiaoyu Yi Yuandong Tao Huixia Zhou Huixia Zhou |
| author_sort | Guang Yue |
| collection | DOAJ |
| description | Obstructive nephropathy is one of the leading causes of kidney injury and fibrosis, which can lead to end-stage renal disease (ESRD). Stromal vascular fraction (SVF), a heterogeneous cell mixture derived from adipose tissue, has been widely used for regenerative medicine across many preclinical models and clinical applications. Recent studies have suggested that SVF can alleviate acute kidney injury in mice. However, to our knowledge, the therapeutic effects of SVF on obstructive nephropathy have not been studied before. In this study, we evaluated the therapeutic potential of SVF on obstructive nephropathy in mice with unilateral ureteral obstruction (UUO). We revealed that autologous SVF administration mitigated UUO-induced renal fibrosis. SVF treatment inhibited both the infiltration of neutrophils and CD4+ T cells, as well as the production of inflammatory cytokines. Moreover, SVF promoted metabolic reprogramming and improved mitochondrial function in the obstructed kidneys, partially through PPAR pathway activation. Mechanistically, SVF-mediated PPAR activation inhibited the epithelial-mesenchymal transition (EMT) process of tubular cells, thus alleviating renal fibrosis in UUO mice. We further confirmed that pharmacological activation of PPAR pathway significantly reduced fibrosis in UUO kidneys. Therefore, our study suggests that SVF may represent a promising therapeutic strategy for obstructive nephropathy. |
| format | Article |
| id | doaj-art-33fa336e9a704c13b1c0c8ce041a86e8 |
| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-33fa336e9a704c13b1c0c8ce041a86e82025-08-20T02:57:36ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-05-011610.3389/fphar.2025.15594461559446Stromal vascular fraction inhibits renal fibrosis by regulating metabolism and inflammation in obstructive nephropathyGuang Yue0Guang Yue1Yunjie Yang2Hongshuai Jia3Hongshuai Jia4Yangyang Wu5Yangyang Wu6Lifei Ma7Xiaoyu Yi8Yuandong Tao9Huixia Zhou10Huixia Zhou11Department of Pediatric Urology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, ChinaMedical School of Chinese PLA, Beijing, ChinaDepartment of Pediatric Surgery, The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, ChinaDepartment of Pediatric Urology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, ChinaMedical School of Chinese PLA, Beijing, ChinaDepartment of Pediatric Urology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, ChinaMedical School of Chinese PLA, Beijing, ChinaDepartment of Pediatric Urology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Pediatric Urology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Pediatric Urology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Pediatric Urology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, ChinaMedical School of Chinese PLA, Beijing, ChinaObstructive nephropathy is one of the leading causes of kidney injury and fibrosis, which can lead to end-stage renal disease (ESRD). Stromal vascular fraction (SVF), a heterogeneous cell mixture derived from adipose tissue, has been widely used for regenerative medicine across many preclinical models and clinical applications. Recent studies have suggested that SVF can alleviate acute kidney injury in mice. However, to our knowledge, the therapeutic effects of SVF on obstructive nephropathy have not been studied before. In this study, we evaluated the therapeutic potential of SVF on obstructive nephropathy in mice with unilateral ureteral obstruction (UUO). We revealed that autologous SVF administration mitigated UUO-induced renal fibrosis. SVF treatment inhibited both the infiltration of neutrophils and CD4+ T cells, as well as the production of inflammatory cytokines. Moreover, SVF promoted metabolic reprogramming and improved mitochondrial function in the obstructed kidneys, partially through PPAR pathway activation. Mechanistically, SVF-mediated PPAR activation inhibited the epithelial-mesenchymal transition (EMT) process of tubular cells, thus alleviating renal fibrosis in UUO mice. We further confirmed that pharmacological activation of PPAR pathway significantly reduced fibrosis in UUO kidneys. Therefore, our study suggests that SVF may represent a promising therapeutic strategy for obstructive nephropathy.https://www.frontiersin.org/articles/10.3389/fphar.2025.1559446/fullSVFobstructive nephropathyrenal fibrosisinflammationPPAR |
| spellingShingle | Guang Yue Guang Yue Yunjie Yang Hongshuai Jia Hongshuai Jia Yangyang Wu Yangyang Wu Lifei Ma Xiaoyu Yi Yuandong Tao Huixia Zhou Huixia Zhou Stromal vascular fraction inhibits renal fibrosis by regulating metabolism and inflammation in obstructive nephropathy Frontiers in Pharmacology SVF obstructive nephropathy renal fibrosis inflammation PPAR |
| title | Stromal vascular fraction inhibits renal fibrosis by regulating metabolism and inflammation in obstructive nephropathy |
| title_full | Stromal vascular fraction inhibits renal fibrosis by regulating metabolism and inflammation in obstructive nephropathy |
| title_fullStr | Stromal vascular fraction inhibits renal fibrosis by regulating metabolism and inflammation in obstructive nephropathy |
| title_full_unstemmed | Stromal vascular fraction inhibits renal fibrosis by regulating metabolism and inflammation in obstructive nephropathy |
| title_short | Stromal vascular fraction inhibits renal fibrosis by regulating metabolism and inflammation in obstructive nephropathy |
| title_sort | stromal vascular fraction inhibits renal fibrosis by regulating metabolism and inflammation in obstructive nephropathy |
| topic | SVF obstructive nephropathy renal fibrosis inflammation PPAR |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1559446/full |
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