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<p>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 <i>Lars1</i><sup>+/−</sup> 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.</p> Graphical abstract <p></p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月21日

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  • Rui Guo,
  • Mei-ni Chen,
  • Qian-hui Lin,
  • Hui-min Qi,
  • Xiao-qi Wang,
  • Bing-yu Li,
  • Shuo Wang,
  • Su-juan Xu,
  • Yue Zhang,
  • Wei Liu

摘要

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.

Graphical abstract