Abstract
Acute kidney injury (AKI) leads to a worse prognosis in diabetic patients compared with prognoses in non-diabetic patients, but whether and how diabetes affects kidney repair after AKI remains unknown. Here, we used scratch-wound healing and transwell migration models to examine whether and how wound healing is affected by high glucose levels in cultured kidney proximal tubular cells (RPTC). The results show that scratch-wound healing and transwell migration were significantly slower in high-glucose-treated kidney tubular cells (30 mM glucose) than in low-glucose-treated cells (5.5 mM). Toll-like receptor 4 (TLR4), MyD88, phospho-protein kinase C (PKC), phospho-p38 MAPK and monocyte chemoattractant protein-1 (MCP-1) mRNA levels were upregulated after high glucose treatments. Staurosporine, a selective PKC inhibitor, inhibited TLR4, MyD88 and p-p38 upregulation in the high-glucose-treated cells, indicating the involvement of PKC in high-glucose-induced TLR4 upregulation. The pharmacological inhibition of TLR4 or shRNA-mediated TLR4 knockdown improved wound healing and transwell migration in high-glucose-treated RPTC. In contrast, the overexpression of TLR4 in low-glucose-treated RPTC suppressed wound healing, mimicking the effects of high glucose levels. These results suggest that the upregulation of TLR4 expression via PKC activation contributes to defective wound healing in high-glucose-treated kidney tubular cells.
Highlights
Acute kidney injury (AKI) leads to significantly lower recovery rates and higher mortality rates in diabetic patients compared with rates in non-diabetic patients[1]
We examined the effect of high glucose levels in a scratch-wound healing model of cultured kidney tubular cells, including rat kidney proximal tubular cells (RPTC), NRK-52E and HEK 293 cells
Our recently published research demonstrates that renal ischemia and reperfusion induced more severe AKI in diabetic mice than in nondiabetic mice and that the severity of AKI is correlated with their blood glucose levels[3]
Summary
Acute kidney injury (AKI) leads to significantly lower recovery rates and higher mortality rates in diabetic patients compared with rates in non-diabetic patients[1]. Recent research has gained significant insight into the mechanism underlying these trends. Goor et al demonstrated the greater vulnerability of STZ-induced diabetic rats to ischemic AKI[2], and our recent study demonstrates that renal ischemia-reperfusion induces more severe AKI in diabetic mice than in nondiabetic mice and that the severity of AKI in these mice is correlated. TLR4 and kidney repair in diabetes with their blood glucose levels[3]. While the pathophysiology of AKI includes kidney tubular cell death and repair[4], most studies have just focused on tubule death, and kidney repair after AKI has received much less attention. Whether and how kidney repair after AKI is affected by high glucose levels has not been clarified
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