Decreased TRPM7 alleviates high glucose-induced renal tubular epithelial cell injury by inhibiting the HMGB1/TLR4 signaling pathway

Abstract

Objective: To explore the regulatory mechanism of transient receptor potential melastatin-7 (TRPM7) in high glucose-induced renal tubular epithelial cell injury. Methods: The expression of TRPM7 in the serum of diabetic nephropathy patients and high glucose-induced HK-2 cells was detected by RT-qPCR. Then, the TRPM7 interference vector was constructed, and the downstream high mobility group box 1 (HMGB1)/Toll-like receptor 4 (TLR4) signaling pathway proteins were detected. Next, in addition to interference with TRPM7 expression, overexpression of HMGB1 in high glucose-induced HK-2 cells was performed. Cell activity, apoptosis, oxidative stress levels, and inflammation levels were determined by CCK8, TUNEL, Western blotting, immunofluorescence and related kits. Results: TRPM7 expression was upregulated in the serum of diabetic nephropathy patients and high glucose-induced HK-2 cells. Interference with TRPM7 reduced cell damage, epithelial-mesenchymal transition, oxidative stress, and inflammatory response in high glucose-induced HK-2 cells via inhibiting the HMGB1/TLR4 signaling pathway. However, the effects induced by TRPM7 silencing were abrogated by HMGB1 overexpression. Conclusions: Decreased TRPM7 alleviates high glucose-induced renal tubular epithelial cell injury by inhibiting the HMGB1/TLR4 signaling pathway. Further animal experiments and clinical trials are warranted to verify its effect.

Keywords

Diabetic nephropathy / TRPM7 / HMGB1/TLR4 / High glucose / Renal tubular epithelial cell

Conflict of interest statement

The authors declare that there is no conflict of interest.

Funding

The authors received no extramural funding for the study.

Authors’ contributions

HC and FMG wrote the manuscript and analyzed the data. HC, FMG, and ZYC performed the experiments and supervised the study. WF searched the literature and revised the manuscript for important intellectual content. HC confirmed the authenticity of all the raw data.

Publisher’s note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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