Polo-Like Kinase 2 Is Identified in Hypertrophy, Extracellular Matrix Accumulation, and Oxidative Stress of Mesangial Cells in Diabetic Nephropathy through p38-MAPK Signaling

Objective: The dysfunction of mesangial cells is a key contributor to the pathogenesis of diabetic nephropathy, while the underlying molecular basis is not fully elucidated.

Methods: Mouse mesangial cells were administered with high glucose medium and the expression of polo-like kinase 2 (PLK2) was determined by PCR and western blot. Loss-of- and gain-of-function of PLK2 was achieved by small interfering RNA targeting PLK2 or PLK2 overexpression plasmid transfections. The hypertrophy, extracellular matrix production, and oxidative stress of mesangial cells were detected. The activation of p38-MAPK signaling was tested using western blot. SB203580 was employed to block the p38-MAPK signaling. The expression of PLK2 in human renal biopsies was detected by immunohistochemistry.

Results: High glucose administration upregulated the expression of PLK2 in mesangial cells. PLK2 knockdown reversed the hypertrophy, extracellular matrix production, and oxidative stress induced by high glucose in mesangial cells. PLK2 knockdown suppressed the activation of p38-MAPK signaling. Blockade of p38-MAPK signaling by SB203580 abolished the dysfunction of mesangial cells induced by high glucose and PLK2 overexpression. The enhanced expression of PLK2 was validated in human renal biopsies.

Conclusion: PLK2 is a key participant in high glucose-induced mesangial cell dysfunction, and might play a crucial role in the pathogenesis of diabetic nephropathy.