2. Academic Validation
  3. LARS1 Promotes Tubular Epithelial Cells Epithelial Mesenchymal Transition in Chronic Kidney Disease by Inhibiting Lipophagy

LARS1 Promotes Tubular Epithelial Cells Epithelial Mesenchymal Transition in Chronic Kidney Disease by Inhibiting Lipophagy

  • Inflammation. 2025 May 21. doi: 10.1007/s10753-025-02313-5.
Rui Guo 1 2 3,  Mei-Ni Chen 1 2,  Qian-Hui Lin 1 2,  Hui-Min Qi 1 2,  Xiao-Qi Wang 1 2,  Bing-Yu Li 1 2,  Shuo Wang 1 2,  Su-Juan Xu 4,  Yue Zhang 5,  Wei Liu 6 7 8
Affiliations

Affiliations

  • 1 Department of Pathology, Key Laboratory of Kidney Diseases of Hebei Province, Hebei Medical University, Shijiazhuang, 050017, China.
  • 2 Center of Metabolic Diseases and Cancer Research, Institute of Medical and Health Science, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang, 050017, Hebei Province, China.
  • 3 Department of Pathophysiology, Hebei North University, Zhangjiakou, 075000, China.
  • 4 Department of Nephrology, Third Hospital of Hebei Medical University, Shijiazhuang, 050017, Hebei Province, China.
  • 5 Department of Diagnostics, Hebei Medical University, No. 361 Zhongshan East Rd, Shijiazhuang, 050017, Hebei Province, China. zhyue@hebmu.edu.cn.
  • 6 Department of Pathology, Key Laboratory of Kidney Diseases of Hebei Province, Hebei Medical University, Shijiazhuang, 050017, China. weiliu929@hebmu.edu.cn.
  • 7 Center of Metabolic Diseases and Cancer Research, Institute of Medical and Health Science, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang, 050017, Hebei Province, China. weiliu929@hebmu.edu.cn.
  • 8 Hebei Key Laboratory of Forensic Medicine, Hebei Province, Shijiazhuang, 050017, China. weiliu929@hebmu.edu.cn.
PMID: 40397353 DOI: 10.1007/s10753-025-02313-5
Abstract

Tubulointerstitial fibrosis (TIF), a critical pathological hallmark in progressive chronic kidney disease (CKD), may be potentiated by renal lipid metabolism dysregulation and ectopic lipid deposition, though these processes likely exhibit bidirectional interactions with fibrotic progression Lipophagy is a type of selective Autophagy that specifically recognizes lipid droplets and is accountable for lipid stability and metabolism. It serves as a link between lipid metabolism and Autophagy. It was found that a positive correlation between elevated LARS1 expression and the severity of renal interstitial fibrosis in CKD patients. In Lars1+/- mice, we observed that the absence of LARS1 significantly reduced lipid deposition and TIF. Mechanistically, stimulation of HK-2 cells with TGF-β1 resulted in LARS1-mediated activation of mTORC1 and suppression of lipophagy, consequently leading to increased lipid accumulation and epithelial mesenchymal transition (EMT) through a defined mechanistic pathway. Collectively, our studies demonstrate that LARS1 plays a pivotal role in renal fibrosis at least in part by inhibiting lipophagy, suggesting that targeting LARS1 may represent a novel therapeutic strategy for patients with CKD.

Keywords

CKD; EMT; LARS1; Lipid deposition; Lipophagy.

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