Kidney Week

Abstract: TH-PO0210

Nuclear FAM3A Alleviates Renal Fibrosis via the PURB-PPARα Axis to Regulate Fatty Acid Metabolism

Session Information

• CKD: Mechanisms of Injury and Fibrosis - 1
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2203 CKD (Non-Dialysis): Mechanisms

Authors

• Wu, Yong, Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, Institute of Nephrology, The Second Xiangya Hospital at Central South University, Changsha, Hunan, China

Yong Wu

• Feng, Baiyu, Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, Institute of Nephrology, The Second Xiangya Hospital at Central South University, Changsha, Hunan, China

Baiyu Feng

• Jiang, Zhuoyuan, Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, Institute of Nephrology, The Second Xiangya Hospital at Central South University, Changsha, Hunan, China

Zhuoyuan Jiang

• Zeng, Yao, Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, Institute of Nephrology, The Second Xiangya Hospital at Central South University, Changsha, Hunan, China

Yao Zeng, MD

• Gao, Yanan, Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, Institute of Nephrology, The Second Xiangya Hospital at Central South University, Changsha, Hunan, China

Yanan Gao, MBBS, MSc

• Yan, Shuxiang, Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, Institute of Nephrology, The Second Xiangya Hospital at Central South University, Changsha, Hunan, China

Shuxiang Yan, MS

• Xu, Weiming, Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, Institute of Nephrology, The Second Xiangya Hospital at Central South University, Changsha, Hunan, China

Weiming Xu, MA

• Ye, Lin, Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, Institute of Nephrology, The Second Xiangya Hospital at Central South University, Changsha, Hunan, China

Lin Ye, MD

• Chen, Changhan, National Medical Metabolomics International Collaborative Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China

Changhan Chen

• Xia, Yang, National Medical Metabolomics International Collaborative Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China

Yang Xia

• Chen, Anqun, Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, Institute of Nephrology, The Second Xiangya Hospital at Central South University, Changsha, China

Anqun Chen, MD, PhD

Background

Impaired fatty acid oxidation (FAO) and energetic stress in proximal tubular epithelial cells are central drivers of renal fibrogenesis. FAM3A has been implicated in mitochondrial energy regulation in metabolically active tissues, but whether FAM3A controls tubular lipid metabolism in chronic kidney disease (CKD) remains unknown.

Methods

FAM3A expression was assessed in human fibrotic kidneys, public single-cell transcriptomic datasets, and murine models of renal fibrosis. Proximal tubule-specific Fam3a loss- and gain-of-function approaches were used to define its role in kidney injury. Untargeted metabolomics, bulk RNA sequencing, and single-cell transcriptomic analyses were integrated to identify FAM3A-regulated pathways. Subcellular localization, co-immunoprecipitation, luciferase reporter assays, and ChIP-qPCR were performed to determine the nuclear mechanism of FAM3A.

Results

FAM3A was markedly reduced in proximal tubular cells from patients with fibrotic CKD and in experimental models of renal fibrosis. Proximal tubule-specific Fam3a deletion aggravated tubular injury, lipid accumulation, and interstitial fibrosis, whereas FAM3A overexpression preserved tubular integrity and attenuated fibrotic remodeling. Multi-omic analyses revealed that loss of FAM3A suppressed a PPARα-centered FAO program, accompanied by lipid deposition and energetic stress. Mechanistically, FAM3A contained a functional nuclear localization signal and translocated to the nucleus, where it interacted with the noncanonical transcription factor PURB. Nuclear FAM3A relieved PURB-mediated repression of the PPARα promoter, restored FAO gene expression, limited lipid accumulation, and suppressed profibrotic tubular reprogramming.

Conclusion

FAM3A preserves proximal tubular metabolic homeostasis and protects against renal fibrosis. These findings identify a previously unrecognized nuclear FAM3A–PURB–PPARα axis that links transcriptional control to FAO maintenance in CKD and support FAM3A as a potential therapeutic target for fibrotic kidney disease.

Funding

• Government Support – Non-U.S.