Resveratrol inhibits progression of IgA nephropathy in rats by inhibiting proliferation of mesangial cells and down regulating expression of PDGF-B and TGF-β1 / 中国药理学通报

Aim To investigate the therapeutic effect of SirTl agonist resveratrol on IgA nephropathy rats and its mechanisms. Methods An IgA nephropathy rat model was established. The rats were divided into four groups randomly: control group, IgA nephropathy group, control treated with Res group and IgA nephropathy treated with Res group. The urine protein was detected by Ponceau S; the biochemical indexes were detected by automatic biochemical analyzer; the pathological changes of kidney were observed by PAS and Masson staining; IgA deposition was observed by immunofluorescence; the expressions of PDGF-B and TGF-fil were detected by immunohistochemistry. Results Compared with IgA nephropathy group, the volume of 24-hour urinary protein and the expression of BUN and Scr in Res group decreased significantly, and the fluorescence of IgA in glomerulus was less in resveratrol group; mesangial cells and matrix proliferated and glomerular volume increased in IgA nephropathy group at the later stage, and both of them were significantly inhibited. Resveratrol could significantly reduce the high expression of PDGF-B and TGF-β1 in IgA nephropathy group. Conclusions Res can inhibit the deposition of IgA immune complex in mesangial region of IgA nephropathy rats and reduce glomerulosclerosis by down-regulating the expression of PDGF-B and TGF-β1, in turn it suppresses cell proliferation in mesangial region. It suggests that resveratrol plays an important role in slowing down the progression of IgA nephropathy.

Mechanisms of rapamycin on regulating rat mesangial cell proliferation and cell cycle through mTORC1/p70S6K pathways / 药学学报

To explore the affect and mechanisms of rapamycin on mesangial cell proliferation and cell cycle, rat mesangial cells (HBZY-1) were cultured and divided into the six groups: normal; normal with platelet derived growth factor (PDGF) 20 ng·mL-1; PDGF + rapamycin 1, 10, 100, 1 000 nmol·L-1. The cell proliferation was measured by MTT in 24 and 48 h; flow cytometry was used to detect the cell cycle phase. Western blot was performed to determine cyclin D1,cyclin E, cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4), p27, p70S6K/p-p70S6K protein expression. The p27 mRNA was detect by Real-time PCR. The results showed that rapamycin significantly suppressed PDGF induced glomerular mesangial cells (MCs) proliferation in a dose and time-dependent manner, but with the dose increased (1 to 1 000 nmol·L-1), the time dependence gradually weakened. Rapamycin inhibited mesangial cell proliferation and arrested the cell cycle in the G0/G1 phase. PDGF at 20 ng·mL-1 significantly increased the expression of cyclin D1, cyclin E and CDK2, CDK4 (P < 0.05), but rapamycin did not affect the expression of cyclin D1, cyclin E and CDK2, CDK4. Rapamycin can significantly inhibited p70S6K phosphorylation, up-regulated the expression of p27 protein and mRNA. Collectively, rapamycin has the effect of inhibiting the glomerular mesangial cells proliferation of mesangial cells by regulating the transcription of p27 mRNA, increasing its protein expression through the mTORC1/p70S6K pathway, resulting in decreased activity of cyclin-CDK, and blocking cell cycle in G0/G1 phase.