engleski

Molecular mechanisms of the renoprotective effect of liraglutide on LLC-PK1 cellular model of proximal tubular cells

Transforming growth factor-beta (TGF-β) has recently been associated with diabetic nephropathy (DN) development. It causes cell apoptosis induced by oxidative stress and cell proliferation and migration triggered by hyperglycemia and inflammation. Liraglutide is an antihyperglycemic agent that has a direct renoprotective effect. This study aimed to evaluate the effects of liraglutide on cell viability and TGF-β expression in the LLC-PK1 model of DN. Cell viability was determined by colorimetric MTT assay and erythrosine B color exclusion assay. The expression of mRNA TGF- β1 was measured by RT-PCR and β-actin was used as an internal control. LLC- PK1 cell culture was treated with different concentrations of glucose (1.5, 30 mM) and the combination of glucose and H2O2 (0.5 mM) for 24 hours. To study the renal effect of liraglutide, cells were treated for 24 hours with different combinations of glucose and liraglutide (10, 20 nM) and combinations of glucose, H2O2, and liraglutide. A significant decrease in MTT levels compared to control (p < 0.01 ; p < 0.001) was observed after treatment with a combination of HG30/ H2O2 and HG30 alone. Cell viability was improved by the addition of liraglutide (10 nM) to cells treated with HG30, while 20 nM had no effect. There was no significant difference in cell survival with the addition of HG30 and HG30/ H2O2 compared to control. The addition of liraglutide at both concentrations to cells treated with HG30 and HG30/H2O2 improved cell survival, although significance was only numerical, not reaching statistical significance. TGF-β1 expression levels were significantly increased in cells treated with HG30 (p < 0.001). Liraglutide inhibited TGF-β1 expression except in HG30/H2O2 treated cells. Our results support a protective role of liraglutide in LLC-PK1 cells, mediated by inhibition of TGF-β1, thus reducing oxidative stress damage.

diabetic nephropathy ; LLC-PK1 cells ; liraglutide

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