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Updated: May 22, 2026
Modeling Hypoxia/Reoxygenation Injury in Proximal Tubular Epithelial Cells
Published on: November 21, 2025
Potential Protective Effect of All-trans Retinoic Acid Against Hypoxia Induced Injury in Renal Tubular Epithelial
Wenshan Lin1, Wenmin Chen1, Shujun Lin1
1Department of Nephrology, The Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China.
Background:
Acute kidney injury (AKI) involves inflammatory infiltration and renal tubular epithelial cells (RTECs) damage. Maladaptive repair post-AKI may lead to chronic kidney disease. All-trans retinoic acid (ATRA) shows protective effects against renal fibrosis, but its mechanism remains unclear. This study investigated whether ATRA alleviates RTECs injury induced by oxygen and glucose deprivation/ reperfusion (OGD/R) and whether it was associated with the RARα/RXRα-LMX1B pathway.
Methods:
An OGD/R model was established using NRK-52E cells, divided into four groups: normal control (NC), OGD/R, Dimethyl sulfoxide (DMSO)+OGD/R, and ATRA+OGD/R. Cell morphology, viability (Cell Counting Kit-8 assay), apoptosis (flow cytometry), and protein levels (Western blot) of transforming growth factor-beta 1 (TGF-β1), α-smooth muscle actin (α-SMA)， retinoic acid receptor alpha (RARα), retinoid X receptor alpha (RXRα), and LIM homeobox transcription factor 1-beta (LMX1B) were assessed. All experiments were independently repeated three times.
Results And Discussion:
OGD/R treatment caused significant cell damage, reduced cell viability, and increased cell apoptosis rate compared to the NC group. The protein expressions of TGF-β1 and α-SMA in the OGD/R group were significantly higher than those in the NC group (p<0.05), but decreased after being pretreated with ATRA (p<0.05). The protein expressions of RARα, RXRα, and LMX1B were downregulated after being treated with OGD/R (p<0.05). In the ATRA+OGD/R group, the expressions of RARα and LMX1B increased (p<0.05), while the expression of RXRα was further reduced (p<0.05) when compared to the DMSO+OGD/R group. Correlation analysis showed that the protein expressions of RARα, RXRα, and LMX1B were not only negatively correlated with TGF-β1 (r=-0.643, -0.879, -0.839, p<0.05), but also with α- SMA (r=-0.755, -0.894, -0.816, p<0.05). LMX1B was positively correlated with RARα and RXRα (r=0.766, 0.776, p<0.05), while RARα was also positively correlated with RXRα (r=0.755, p<0.05).
Conclusion:
ATRA mitigates hypoxia-induced RTECs injury and was associated with the expressions of RARα, RXRα, and LMX1B.
