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Rapamycin Inhibits Platelet-Derived Growth Factor-Induced Collagen, but Not Fibronectin, Synthesis in Rat Mesangial Cells

 Myoung Soo Kim  ;  Jehyun Park  ;  Chul Woo Yang  ;  Duk Hee Kang  ;  Hyeon Joo Jeong  ;  Shin Wook Kang  ;  Yu Seun Kim  ;  Hunjoo Ha 
 YONSEI MEDICAL JOURNAL, Vol.45(6) : 1121-1126, 2004 
Journal Title
Issue Date
Animals ; Cells, Cultured ; Collagen/antagonists & inhibitors* ; Collagen/biosynthesis ; Fibronectins/biosynthesis* ; Glomerular Mesangium/cytology ; Glomerular Mesangium/drug effects ; Glomerular Mesangium/metabolism* ; Immunosuppressive Agents/pharmacology* ; Male ; Platelet-Derived Growth Factor/pharmacology* ; Rats ; Rats, Sprague-Dawley ; Sirolimus/pharmacology*
Rapamycin ; mesangial cell ; collagen ; fibronectin
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 10 ng/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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1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kang, Shin Wook(강신욱) ORCID logo https://orcid.org/0000-0002-5677-4756
Kim, Myoung Soo(김명수) ORCID logo https://orcid.org/0000-0002-8975-8381
Kim, Yu Seun(김유선) ORCID logo https://orcid.org/0000-0002-5105-1567
Jeong, Hyeon Joo(정현주) ORCID logo https://orcid.org/0000-0002-9695-1227
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