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Rapamycin inhibits platelet-derived growth factor-induced collagen, but not fibronectin, synthesis in rat mesangial cells

Title
Rapamycin inhibits platelet-derived growth factor-induced collagen, but not fibronectin, synthesis in rat mesangial cells
Authors
Kim M.S.Park J.Ha H.Kim Y.S.Kang S.-W.Jeong H.J.Kang D.-H.Yang C.W.
Ewha Authors
강덕희하헌주
SCOPUS Author ID
강덕희scopus; 하헌주scopus
Issue Date
2004
Journal Title
Yonsei Medical Journal
ISSN
0513-5796JCR Link
Citation
vol. 45, no. 6, pp. 1121 - 1126
Indexed
SCI; SCIE; SCOPUS; KCI WOS scopus
Abstract
Rapamycin, a macrocyclic lactone, is effective in reducing the incidence of acute rejection after renal transplantation. The inhibitory effects of rapamycin on lymphocyte proliferation and the molecular mechanisms that were involved have been described. However, its effects on glomerular mesangial cells have not been clearly understood, and here, we examined the effect of rapamycin on platelet-derived growth factor (PDGF)-induced extracellular matrix synthesis as well as cell proliferation in mesangial cells. Rat mesangial cells were isolated from the glomeruli of Sprague-Dawley rats and cultured with Dulbecco's modified Eagles medium containing 20% fetal bovine serum. Different concentrations of rapamycin were administered 1 hour before the addition of 10ng/ml of PDGF into growth arrested and synchronized cells. Cell proliferation was assessed by [3H]thymidine incorporation, total collagen synthesis by [3H]proline incorporation, and fibronectin secretion into the medium by Western blot analysis. In the mesangial cells, PDGF increased cell proliferation by 4.6-fold, total collagen synthesis by 1.8-fold, and fibronectin secretion by 3.2-fold. Rapamycin above 10 nM significantly inhibited PDGF-induced proliferation and collagen synthesis, but the treatment of rapamycin up to 1 μM did not show any significant effects on PDGF-induced fibronectin secretion. These inhibitory effects of rapamycin on PDGF-induced mesangial cell proliferation and collagen synthesis reflect the potential value of rapamycin in the prevention and treatment of glomerulosclerosis in patients with chronic allograft nephropathy.
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의학전문대학원 > 의학과 > Journal papers
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