Prolyl hydroxylase-2 (EGLN1) mediates TGF-β1 pathway regulated epithelial-mesenchymal transition in yak kidneys

Epithelial-mesenchymal transition (EMT) is a pivotal process in renal fibrosis and various kidney disorders, with hypoxia recognized as a key trigger. Yaks, having adapted to high-altitude, hypoxic environments over generations, exhibit unique hypoxia adaptation mechanism. However, it remains unclear whether hypoxia promotes EMT in yak kidneys. In this study, we demonstrated that hypoxia did not induce EMT in yak kidneys. By inducing hypoxia in yak renal tubular epithelial cells (RTECs), we observed that chronic hypoxia inhibited the protein expression of N-cadherin and Fibronectin while upregulating E-cadherin expression. This suggests that chronic hypoxia suppresses EMT in yak kidneys. To further investigate the underlying mechanism, we conducted RNA-Seq analysis on hypoxia-treated RTECs, which revealed that the prolyl hydroxylase-2 (EGLN1) and the TGF-β1 pathway might play central roles in this process. Subsequently, we confirmed that activation of the TGF-β1 pathway can induce EMT. We also provided evidence that overexpression or knockdown of EGLN1 inhibited or enhanced, respectively, TGF-β1-induced EMT-specific protein expression in RTECs. Additionally, EGLN1 effectively suppresses RTEC migration while promoting cell proliferation under hypoxic conditions. These findings suggest that yaks may protect their kidneys from hypoxia-induced EMT by upregulating the expression of EGLN1 under chronic hypoxia.