2. Academic Validation
  3. Apelin-36 attenuates diabetic glomerular endothelial hyperpermeability via the KLF2/Occludin pathway

Apelin-36 attenuates diabetic glomerular endothelial hyperpermeability via the KLF2/Occludin pathway

  • Peptides. 2026 Mar:196:171472. doi: 10.1016/j.peptides.2026.171472.
Jinxiao Jiang 1,  Liu Yang 2,  Yuhao Cheng 3,  Meiqin Xiong 4,  Xiaoqin Zhou 5
Affiliations

Affiliations

  • 1 Department of Nephrology, Huanggang Central Hospital, Huanggang, Hubei 438000, China.
  • 2 Bishan Hospital of Chongqing Medical University, Bishan Hospital of Chongqing, Chongqing 402760, China.
  • 3 Department of Nephrology, Xishui County People's Hospital, Huanggang, Hubei 438299, China.
  • 4 Department of Nephrology, Qianjiang Central Hospital of Hubei province, Qianjiang, Hubei 433100, China. Electronic address: [email protected].
  • 5 Bishan Hospital of Chongqing Medical University, Bishan Hospital of Chongqing, Chongqing 402760, China. Electronic address: [email protected].
PMID: 41690598 DOI: 10.1016/j.peptides.2026.171472
Abstract

An increase in glomerular endothelial cell (GEC) permeability is an early trigger for diabetic nephropathy (DN). This study investigated the protective role of the Apelin-36/APJ axis under diabetic conditions. In vitro, high glucose (HG) downregulated APJ expression and secretion of Apelin-36 in human renal glomerular endothelial cells (HRGECs) in a time-dependent manner and induced endothelial hyperpermeability. Apelin-36 treatment dose-dependently mitigated this hyperpermeability, restored the expression of Occludin and Krüppel-like factor 2 (KLF2) suppressed by HG, and activated the Apelin/APJ system. KLF2 knockdown or pharmacological APJ inhibition abolished the protective effects of Apelin-36. In vivo, Apelin-36 treatment ameliorated albuminuria, restored glomerular Occludin expression, and partially rescued the disrupted Apelin/APJ axis in db/db mice. These findings demonstrate that the Apelin-36/APJ axis protects against glomerular endothelial dysfunction in DN via the KLF2/Occludin pathway, highlighting its potential as a therapeutic target for diabetic renal injury, particularly in the glomerular endothelium.

Keywords

Apelin-36; Diabetic nephropathy; High glucose; Hyperpermeability; Occludin.

Figures
Products