2. Academic Validation
  3. The Limb-bud and Heart (LBH) promotes renal fibrosis through endoplasmic reticulum stress-induced pyroptosis and partial epithelial-mesenchymal transition in renal tubular epithelial cells

The Limb-bud and Heart (LBH) promotes renal fibrosis through endoplasmic reticulum stress-induced pyroptosis and partial epithelial-mesenchymal transition in renal tubular epithelial cells

  • Cell Signal. 2026 May:141:112359. doi: 10.1016/j.cellsig.2026.112359.
Tao Shu 1,  Ning Luo 2,  Yuqi Shu 3,  Jingyan Wei 1,  Hongxin Niu 4,  Qicai Liu 5
Affiliations

Affiliations

  • 1 Department of General Practice, Zhujiang Hospital, Southern Medical University, 253# Middle Industrial Avenue, Guangzhou, Guangdong 510280, PR China.
  • 2 Department of Nephrology, NHC Key Laboratory of Clinical Nephrology, Guangdong Provincial Key Laboratory of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, 58th Zhongshan Road II, Guangzhou, Guangdong 510080, PR China.
  • 3 Department of Cardiology, Laboratory of Heart Center; Guangdong Engineering Technology Research Center of Biomedicine for Cardiovascular Disease, Zhujiang Hospital, Southern Medical University, 253# Middle Industrial Avenue, Guangzhou, Guangdong 510080, PR China.
  • 4 Department of General Practice, Zhujiang Hospital, Southern Medical University, 253# Middle Industrial Avenue, Guangzhou, Guangdong 510280, PR China. Electronic address: [email protected].
  • 5 Department of Cardiology, Laboratory of Heart Center; Guangdong Engineering Technology Research Center of Biomedicine for Cardiovascular Disease, Zhujiang Hospital, Southern Medical University, 253# Middle Industrial Avenue, Guangzhou, Guangdong 510080, PR China. Electronic address: [email protected].
PMID: 41520745 DOI: 10.1016/j.cellsig.2026.112359
Abstract

Renal fibrosis is a primary pathological feature of chronic kidney disease, with a current lack of effective treatments. In this study, we observed that Limb-bud and Heart (LBH) expression was upregulated in kidney specimens obtained from patients with chronic kidney disease. During UUO-induced renal fibrosis, both the protein level and mRNA level of LBH were significantly elevated. Furthermore, knockout of the mouse LBH gene significantly ameliorated renal fibrosis. The application of inhibitors, agonists, and knockout mouse models uniformly verified the role of LBH deficiency in alleviating both endoplasmic reticulum stress (ERS) and Pyroptosis. Although renal tubular epithelial cells (RTECs) are conventionally considered the initial responders to renal fibrosis, the role and mechanism of LBH in these cells during disease progression remain unclear. Therefore, this study focused on investigating LBH's effects in damaged RTECs. Mechanistic studies demonstrated that within renal tubular epithelial cells, LBH significantly promotes renal fibrosis by forming a positive feedback loop with TGFβ1 and ERS. This activated ERS subsequently further induces Pyroptosis and partial epithelial-mesenchymal transition (pEMT), thereby promoting renal fibrosis. Importantly, LBH deficiency was shown to significantly attenuate renal fibrosis. These collective findings strongly suggest that LBH may constitute a promising therapeutic target for the treatment of renal fibrosis.

Keywords

ERS; LBH; Pyroptosis; Renal fibrosis; pEMT.

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