Hao Ding;Feng Bai;Hongdi Cao;Jing Xu;Li Fang;Jining Wu;Qi Yuan;Yang Zhou;Qi Sun;Weichun He;Chunsun Dai;Ke Zen;雷 江;Junwei Yang
Nanjing Medical University;Xuzhou Medical University;Nantong University;Nanjing University;China Association for Science and Technology
发表时间:2018-9-1
期 刊:Antioxidants and Redox Signaling
语 言:English
U R L: http://www.scopus.com/inward/record.url?scp=85050668516&partnerID=8YFLogxK
Aims: Cyclic adenosine 3′5′-monophosphate (cAMP) is a universal second messenger that plays an important role in intracellular signal transduction. cAMP is synthesized by adenylate cyclases from adenosine triphosphate and terminated by the phosphodiesterases (PDEs). In the present study, we investigated the role of the cAMP pathway in tubular epithelial cell mitochondrial biogenesis in the pathogenesis of renal fibrosis. Results: We found that the cAMP levels were decreased in fibrotic kidney tissues, and replenishing cAMP could ameliorate tubular atrophy and extracellular matrix deposition. The downregulation of cAMP was mainly attributed to the increased PDE4 expression in tubular epithelial cells. The inhibition of PDE4 by PDE4 siRNA or the specific inhibitor, rolipram, attenuated unilateral ureteral obstruction-induced renal interstitial fibrosis and transforming growth factor (TGF)-β1-stimulated primary tubular epithelial cell (PTC) damage. The Epac1/Rap1 pathway contributed to the main effect of cAMP on renal fibrosis. Rolipram could restore C/EBP-β and PGC-1α expression and protect the mitochondrial function and structure of PTCs under TGF-β1 stimulation. The antifibrotic role of rolipram in renal fibrosis relies on C/EBP-β and PGC-1α expression in tubular epithelial cells. Innovation and Conclusion: The results of the present study indicate that cAMP signaling regulates the mitochondrial biogenesis of tubular epithelial cells in renal fibrosis. Restoring cAMP by the PDE4 inhibitor rolipram may ameliorate renal fibrosis by targeting C/EBP-β/PGC1-α and mitochondrial biogenesis. Antioxid. Redox Signal. 29, 637-652.
化合物
医学与生命科学
Scopus度量
年份 | CiteScore | SJR | SNIP |
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1996 | |||
1997 | |||
1998 | |||
1999 | |||
2000 | 0.489 | 0.251 | |
2001 | 0.537 | 0.311 | |
2002 | 1.071 | 0.621 | |
2003 | 1.424 | 0.738 | |
2004 | 1.739 | 0.895 | |
2005 | 1.869 | 0.866 | |
2006 | 1.946 | 0.896 | |
2007 | 2.69 | 1.242 | |
2008 | 3.041 | 1.384 | |
2009 | 3.184 | 1.667 | |
2010 | 3.117 | 1.676 | |
2011 | 11 | 3.353 | 1.932 |
2012 | 13 | 3.434 | 1.764 |
2013 | 13.3 | 3.395 | 1.857 |
2014 | 13.2 | 3.137 | 1.742 |
2015 | 13.4 | 3.066 | 1.597 |
2016 | 15.7 | 2.897 | 1.678 |
2017 | 14.6 | 2.607 | 1.586 |
2018 | 11 | 2.151 | 1.439 |
2019 | 10.7 | 2.163 | 1.56 |
2020 | 11.5 |
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