High Glucose Induces Mouse Mesangial Cell Overproliferation via Inhibition of Hydrogen Sulfide Synthesis in a TLR-4-Dependent Manner

Background/Aims: Overproliferation of mesangial cells was believed to play an important role in the progress of diabetic nephropathy, one of the primary complications of diabetes. Hydrogen sulfide (H2S), a well-known and pungent gas with the distinctive smell of rotten eggs, was discovered to play a protective role in diabetic nephropathy. Methods: MTT assay was used to examine the viability of mesangial cells. Small interfering RNA was used to knock down the expression of TLR4 while specific inhibitor LY294002 to suppress the function of PI3K. H2S generation rate was determined by a H2S micro-respiration sensor. Results: Glucose of 25mM induced significant mesangial cells proliferation, which was accomplished by significantly inhibited endogenous H2S synthesis. And exogenous H2S treatment by NaHS markedly mitigated the overproliferation of mouse mesangial cells. Furthermore, it was found that H2S deficiency could result in TLR4 activation. And H2S supplementation remarkably inhibited TLR4 expression and curbed the mesangial cell overproliferation. Besides, PI3K/Akt pathway inhibition also significantly ameliorated the cell overproliferation. Conclusion: High glucose (HG) induces mouse mesangial cell overproliferation via inhibition of hydrogen sulfide synthesis in a TLR-4-dependent manner. And PI3K/Akt pathway might also play a vital part in the HG-induced mesangial cell overproliferation.