Effects Of Arotinoid Ethylester On Cell Proliferation, Apoptosis And Secretion Of TGF-β1 Of In Mouse Glomerular Mesangial Cells

Background: Systemic lupus erythematiosus (SLE) is a systemic autoimmune disease characterized by a waxing and waning course and the involvement of multiple organs, including skin, kidneys, and central nervous system. Lupus nephritis (LN) is an inflammation of the kidney caused by systemic lupus erythematosus. Glomerular mesangial cell proliferation is one of the main pathologic features in LN. Mesangial cell secrete a large number of matrix and cytokines to promote the process of renal injury and inflammation. With the progression of LN, the renal function of the patients gets worse and worse gradually, even uremia happens, which can lead to death. Current clinical treatments for LN include glucocorticoids and immune-osuppressive agents etc. However, due to adverse effects and bad tolerability of above-mentioned drugs, the curative effect is not so well. Previous studies shows that the first-generation retinoids drugs - all-trans retinoic acid can slow down the procession of LN in SLE mouse model, alleviate the renal pathological damage and reduce the urinary protein. The effects of all-trans retinoic acid on glomerular mesangial cells include inhibiting proliferation, inducing apoptosis and reducing the secretion of a variety of cytokines and extracellular matrix. However, the side effects of the first and the second generation of retinoid agents, such as severe teratogenic effects, liver damage and skin or mucosal dryness, restrict the feasibility of the clinical treatment for LN seriously. The third generation of Victoria with an aromatic acid drugs ring, has a specific selection for retinoid receptor, which can reduce the side effects. In order to investigate the potential of the third-generation of retinoids on the treatment of the renal disease, our group observed the influence of cell proliferation, apoptosis and the secretion of TGF-β1 and IL-6 by arotinoid ethylester in mouse glomerular mesangial cells.Objectives: To investigate the influence of AE on the cell proliferation, apoptosis and the expression of TGF-β1 and IL-6 in mouse glomerular mesangial cells, and observe the differences among the effects of AE, atRA and CTX on the index mentioned above in mouse GMC, for an insight into the potential effect of AE on renal inflamation, especially on LN.Methods: (1) MTT was utilized to assess the influence of AE, atRA and CTX on proliferation of mouse glomerular mesangial cells at different concentration and different time. (2) Apoptosis of mouse glomerular mesangial cells was measured by flow cytometry analysis at different concentrations of AE, atRA and CTX. (3) ELISA was used to detect the concentration of TGF-β1, IL-6 in the culture supernatant of mouse glomerular mesangial cells after different drug inervention at different concentrations.Results: (1) MTT assay showed that AE, atRA and CTX all inhibited GMC proliferation in dose- and time-dependent manner. The influence of AE was more obvious than that of the other two drugs. CTX inhibited the cell proliferation only at high dose. (2) Annexin V/PI FCM demonstrated that AE, atRA and CTX iuduced GMC apoptosiss. The effect of AE was the most obvious among three drugs. (3) ELISA revealed that all the drugs reduced the secretion of TGF-β1, compared with the control cells, but had no significant effect on secretion of IL-6 in mouse glomerular mesangial cells.Conclusions: AE could inhibit cell proliferation, induce cell apoptosis and reduce TGF-β1 secretion in mouse glomerular mesangial cells. AE might intervene with the progression of LN.