Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 36, Issue 5, Pages 1911-1927Publisher
KARGER
DOI: 10.1159/000430160
Keywords
Autosomal dominant polycystic kidney disease (ADPKD); Chronic kidney disease (CKD); cAMP-PKA signaling pathway; Transforming growth factor-beta 1 (TGF-beta 1); Extracellular regulated protein kinase (ERK)
Categories
Funding
- National Natural Science foundation of China [81370783, 81261160507, 81330074, 81170632]
Ask authors/readers for more resources
Background: The cAMP-PKA signaling pathway and TGF-beta 1-dependent fibrosis pathways are of particular importance in ADPKD progression, but the cross-talk between these pathways remains unclear. Therefore, we used an MDCK-cell model and embryonic kidnay-cyst model to study the regulat ory role of cAMP-PKA signaling in the TGF-beta 1 induced fibrotic process.Method and Results: Pkd1(flox/flox); Ksp-Cre and Pkd1(+/+); Ksp-Cre mice were used as an in vivo model. Increased kidney volume, renal cysts formation and up-regulation of thefibrosis-related proteins TGF-beta 11, FN and collagen type I were highly expressed. Western blotting revealed the obviously up-regulation of TGF-beta 1, CTGF, FN and collagen typed I expression following forskolin treatment in MDCK cells. Selective PKA inhibition with H89 may partially reversed the above effects. Pretreatment with the TGF-beta RI kinase inhibitor Vi SB431542 suppressed the increased expression of CTGF,FN and collagen type I caused by forskolin. Our data also indicate that forskolin inhibited TGF-beta-induced ERK1/2 phosphorylation and FN p-regulation. ERK inhibition useing PD98059 significantly inhibited the expression of CTGF,FN and collagen type I causd by TGF-beta 1. Conclusion: The cAMP-PKA signaling pathway can directly promote the production of TGF-beta 1 and/or TGF-beta 1 and its downstream pathways were highly ecpressed MDCK cells, cAMP-PKA had a significantly negative effect on TGF-beta induced p-ERK1/2 and FN expression. Copyright (C) 2015 S. Karger AG, Basel
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available