Platelets induce epithelial to mesenchymal transition in renal proximal tubular epithelial cells through TGF-β signaling pathway

作者：Ukhti Jamil Rustiasari, Melissa Uil, Xiaomeng Zhang, Nike Claessen, Loes M. Butter, Sandrine Florquin, Alessandra Tammaro, Joris J. T. H. Roelofs · 发表于：Molecular Medicine · 年份：2025 · DOI：10.1186/s10020-025-01355-7 · 被引用次数：4 · 研究领域：Chronic Kidney Disease and Diabetes、Dialysis and Renal Disease Management、Acute Kidney Injury Research

BACKGROUND: Management of chronic kidney disease (CKD) remains a major challenge due limited therapeutic options to reverse fibrosis, which is a critical feature in CKD. Partial epithelial-to-mesenchymal transition (EMT) of tubular epithelial cells (TECs) is a key driver of fibrosis, and has become an important focus for kidney protection strategies. Blood platelets, a major source of circulating transforming growth factor beta (TGF-β), are implicated in pathogenesis of CKD, but their involvement in EMT and kidney fibrosis remains uncertain. METHODS: We used two mouse models of renal fibrosis—diabetic kidney disease (DKD) and unilateral ureter obstruction (UUO)—to examine the connection between platelets, partial EMT, and fibrosis. Platelet inhibition or depletion was performed to assess EMT, cell cycle arrest, and fibrosis. In vitro, platelets were applied to TECs and kidney organoids. To determine the role of TGF-β signaling, we used TGF-βRI inhibitor. Expression of EMT, and fibrosis markers, as well as TGF-β1 signaling, were analyzed using western blot, reverse transcription quantitative PCR (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and immunostaining. RESULTS: In both animal models, platelet inhibition or depletion resulted in reduced expression of cell cycle arrest marker p21, partial EMT and fibrosis. In vitro, activated platelets stimulated cell cycle arrest, EMT, and fibrosis in TECs and kidney organoids. Chronically injured TECs experience cell-cycle arre...