title: Mycophenolic acid inhibits the phosphorylation of nuclear factor‑κB and Akt in renal tubular epithelial cells.
abstract: Renal tubulointerstitial injury induced by albumin overload is a critical stage during the progression of renal interstitial fibrosis and progression of chronic renal diseases. Inosine‑5'‑monophosphate dehydrogenase inhibitor mycophenolate mofetil (MMF), a pro‑drug of mycophenolic acid (MPA), is known to attenuate the progression of renal interstitial fibrosis; however, the underlying molecular mechanisms of the anti‑ﬁbrotic effects of derivatives of MMF have not yet been studied. The present study assessed the effects of the MPA on renal tubular epithelial cells. Transforming growth factor beta 1 (TGF‑β1) has been indicated to have a central role in the underlying molecular mechanisms of renal fibrosis; furthermore, nuclear transcription factor‑κB (NF‑κB) is a transcription factor associated with the production of inflammatory cytokines, cell proliferation and apoptosis. In addition, the Akt signaling pathway has important roles in cell proliferation, differentiation, metabolism and apoptosis. The present study subjected the NRK52E rat kidney epithelial‑derived cell line to albumin overload, which resulted in an increase in TGF‑β1 production as well as phosphorylation of Akt and the binding activity of NF‑κB to the promoter region of the TGF‑β1 gene, which was, however, reduced following pre‑incubation of the cells with MPA. In addition, the effects of albumin were partially blocked by Ly294002, a specific inhibitor of Akt. In conclusion, the results of the present study suggested that MPA may exert its anti‑fibrotic effects by inhibiting the upregulation of TGF‑β1 and the activation of NF‑κB following albumin overload, which may be partly dependent on the Akt pathway.
authors.affiliation: Department of Nephrology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zeng
authors.affiliation: Department of Nephrology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Hui-Qun
authors.initials: HQ
authors.lastname: Qin
authors.affiliation: Department of Nephrology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Wei-Jia
authors.initials: WJ
authors.lastname: Xu
authors.affiliation: Department of Nephrology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Ming-Dan
authors.initials: MD
authors.lastname: Zheng
authors.affiliation: Department of Nephrology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Hu
authors.affiliation: Department of Nephrology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Shui
mesh_terms: D000418:Albumins / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D007684:Kidney Tubules / Q000166:cytology*; D009025:Morpholines / Q000494:pharmacology; D009173:Mycophenolic Acid / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000418:Albumins; D002867:Chromones; D009025:Morpholines; D016328:NF-kappa B; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051057:Proto-Oncogene Proteins c-akt; D009173:Mycophenolic Acid