BACKGROUND: Activation of mesangial cells is observed in several forms of chronic renal disease, and in culture conditions upon stimulation by fetal calf serum (FCS), or agonists such as transforming growth factor beta (TGF-beta). Mycophenolate mofetil (MMF), the precursor of mycophenolic acid (MPA), is currently used in organ transplantation and has been shown to be protective in clinical and experimental glomerulonephritis. This study assessed the effects of MPA on markers of human mesangial cells (HMC) activation. METHODS: Primary cultures of HMC and of an immortalized HMC clone (IP15 cells characterized in this report) were stimulated either by FCS or by TGF-beta, and treated by MPA at clinically relevant concentrations (1 to 10 micromol/L) for 24 hours to 14 days. HMC proliferation, smooth muscle alpha-actin (SMA), collagen type I alpha-1 chain (coll I) and fibronectin synthesis were used as markers of HMC phenotypic activation. RESULTS: Exposure of HMC to MPA inhibited proliferation induced by FCS without cytotoxicity. MPA counteracted the stimulatory effects of FCS and TGF-beta on coll I mRNA and protein and fibronectin protein. SMA expression was increased upon exposure to MPA, without cell hypertrophy. CONCLUSION: Treatment of cultured HMC with MPA inhibited mesangial cell proliferation and matrix production induced by stimulation with either FCS or TGF-beta. Such mechanisms may contribute to the favorable effects of treatment using mycophenolate mofetil in chronic fibrotic kidney diseases, including chronic allograft rejection.
BACKGROUND: Activation of mesangial cells is observed in several forms of chronic renal disease, and in culture conditions upon stimulation by fetal calf serum (FCS), or agonists such as transforming growth factor beta (TGF-beta). Mycophenolate mofetil (MMF), the precursor of mycophenolic acid (MPA), is currently used in organ transplantation and has been shown to be protective in clinical and experimental glomerulonephritis. This study assessed the effects of MPA on markers of human mesangial cells (HMC) activation. METHODS: Primary cultures of HMC and of an immortalized HMC clone (IP15 cells characterized in this report) were stimulated either by FCS or by TGF-beta, and treated by MPA at clinically relevant concentrations (1 to 10 micromol/L) for 24 hours to 14 days. HMC proliferation, smooth muscle alpha-actin (SMA), collagen type I alpha-1 chain (coll I) and fibronectin synthesis were used as markers of HMC phenotypic activation. RESULTS: Exposure of HMC to MPA inhibited proliferation induced by FCS without cytotoxicity. MPA counteracted the stimulatory effects of FCS and TGF-beta on coll I mRNA and protein and fibronectin protein. SMA expression was increased upon exposure to MPA, without cell hypertrophy. CONCLUSION: Treatment of cultured HMC with MPA inhibited mesangial cell proliferation and matrix production induced by stimulation with either FCS or TGF-beta. Such mechanisms may contribute to the favorable effects of treatment using mycophenolate mofetil in chronic fibrotic kidney diseases, including chronic allograft rejection.
Authors: Agnes Hackl; Jan U Becker; Lisa M Körner; Rasmus Ehren; Sandra Habbig; Eva Nüsken; Kai-Dietrich Nüsken; Kathrin Ebner; Max C Liebau; Carsten Müller; Martin Pohl; Lutz T Weber Journal: Pediatr Nephrol Date: 2017-11-25 Impact factor: 3.714
Authors: A Kornberg; B Küpper; K Thrum; B Krause; P Büchler; J Kornberg; A Sappler; A Altendorf-Hofmann; J Wilberg; H Friess Journal: Dig Dis Sci Date: 2010-09-08 Impact factor: 3.199
Authors: Kyu Ha Huh; Hyung Joon Ahn; Jehyun Park; Man Ki Ju; Jae Sook Song; Myoung Soo Kim; Soon Il Kim; Yu Seun Kim Journal: Pediatr Nephrol Date: 2008-12-18 Impact factor: 3.714
Authors: Mahesh Jonnalagadda; Christine E Brown; Wen-Chung Chang; Julie R Ostberg; Stephen J Forman; Michael C Jensen Journal: PLoS One Date: 2013-06-06 Impact factor: 3.240