Abstract
Renal fibroblasts play a pivotal role in the development of tubulointerstitial fibrosis, a condition highly predictive of progression towards end-stage renal disease. The present study investigated the anti-mitogenic and anti-inflammatory effects of an inhibitor of inosine monophosphate dehydrogenase, mycophenolic acid (MPA) and the mechanisms underlying its action in normal rat kidney fibroblasts (49F cells). Proliferation of 49F cells was studied by tetrazole 3-(4, 5-dimethylthiazol-2-yl-)-2,5-diphenyltetrazolium bromide (MTT) test, bromodeoxyuridine incorporation and flow cytometry. The cyclins, tumour suppressor genes and phospho-mitogen-activated protein kinases (MAPKs) were semiquantified by immunoblotting. Apoptosis was measured by quantifying the fragmented DNA and the activity of caspase 3. The monocyte chemokine CCL2 was measured by ELISA. The mRNA expression of CCL2 was measured by real-time PCR. Mycophenolic acid dose-dependently inhibited steady-state proliferation of 49F cells by up-regulation of p21, p27 and p53, in association with a decrease in cyclins D2 and E. Treatment with MPA also triggered apoptosis of 49F cells by activating the caspase 3 cascade. Furthermore, MPA attenuated tumour necrosis factor-alpha-...Continue Reading
References
Jul 15, 1994·Cell·H Toyoshima, T Hunter
Dec 9, 1997·The Journal of Pathology·L S Cox
Feb 23, 1999·Kidney International·F RomeroE Tapia
Jul 1, 1999·Genes & Development·C J Sherr, J M Roberts
Jul 8, 2000·Kidney International·C BadidM Laville
Jun 27, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Liang QiaoPaul Dent
Nov 22, 2002·Journal of the American Society of Nephrology : JASN·Shuei-Liong LinTun-Jun Tsai
Dec 11, 2002·Kidney International·Ricardo UtimuraIrene De Lourdes Noronha
Jan 19, 2005·Clinical and Experimental Immunology·M ChiaraD Roccatello
Aug 17, 2005·Current Molecular Medicine·Hirokazu Okada, Raghu Kalluri
Sep 24, 2005·Lupus·H GuoK N Lai
Oct 19, 2005·The International Journal of Biochemistry & Cell Biology·Weier QiCarol A Pollock
Dec 21, 2005·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Alexander S FarivarMichael S Mulligan
Jan 24, 2006·International Immunopharmacology·Yong-Gui WuShan-Tan Lin
Mar 1, 2006·Molecular Cancer Therapeutics·Naoko TakebeGuido Tricot
Apr 13, 2006·Current Opinion in Nephrology and Hypertension·Carla ZojaGiuseppe Remuzzi
Jun 3, 2006·Life Sciences·Hunjoo HaYu Seun Kim
Aug 15, 2006·Transplantation·Andreas BoldtJan F Gummert
Nov 15, 2006·Clinical Transplantation·Christian MorathWalter Muranyi
Feb 21, 2007·Expert Opinion on Biological Therapy·Elena Gagliardini, Ariela Benigni
Feb 27, 2007·Leukemia Research·Gyula VégsoLászló Kopper
Sep 11, 2007·Seminars in Immunopathology·Li-Jun Ma, Agnes B Fogo
Oct 24, 2007·Cellular & Molecular Biology Letters·Takeo YamaguchiShigeyuki Terada
Nov 9, 2007·Kidney International·V SepeA Dal Canton
May 31, 2008·Diabetes·Ying QianFrank C Brosius
Oct 22, 2008·Transplantation Proceedings·J Y KimY S Kim
Nov 4, 2009·British Journal of Pharmacology
Citations
Oct 31, 2013·Clinical & Developmental Immunology·Susan YungTak Mao Chan
Mar 12, 2016·Colloids and Surfaces. B, Biointerfaces·Jangsun HwangJonghoon Choi
Mar 11, 2016·Clinical Reviews in Allergy & Immunology·Susan Yung, Tak Mao Chan
Dec 20, 2014·Proteome Science·Darinka Todorova PetrovaMichael Oellerich