|  Help  |  About  |  Contact Us

Publication : ADAM17 promotes proliferation of collecting duct kidney epithelial cells through ERK activation and increased glycolysis in polycystic kidney disease.

First Author  Beck Gooz M Year  2014
Journal  Am J Physiol Renal Physiol Volume  307
Issue  5 Pages  F551-9
PubMed ID  24899059 Mgi Jnum  J:214249
Mgi Id  MGI:5588621 Doi  10.1152/ajprenal.00218.2014
Citation  Beck Gooz M, et al. (2014) ADAM17 promotes proliferation of collecting duct kidney epithelial cells through ERK activation and increased glycolysis in polycystic kidney disease. Am J Physiol Renal Physiol 307(5):F551-9
abstractText  Polycystic kidney disease (PKD) is a common genetic disorder leading to cyst formation in the kidneys and other organs that ultimately results in kidney failure and death. Currently, there is no therapy for slowing down or stopping the progression of PKD. In this study, we identified the disintegrin metalloenzyme 17 (ADAM17) as a key regulator of cell proliferation in kidney tissues of conditional knockout Ift88(-/-) mice and collecting duct epithelial cells from Ift88 degrees (rpk) mice, animal models of autosomal recessive polycystic kidney disease (ARPKD). Using Western blotting, an enzyme activity assay, and a growth factor-shedding assay in the presence or absence of the specific ADAM17 inhibitor TMI-005, we show that increased expression and activation of ADAM17 in the cystic kidney and in collecting duct epithelial cells originating from the Ift88 degrees (rpk) mice (designated as PKD cells) lead to constitutive shedding of several growth factors, including heparin-binding EGF-like growth factor (HB-EGF), amphiregulin, and transforming growth factor-alpha (TGF-alpha). Increased growth factor shedding induces activation of the EGFR/MAPK/ERK pathway and maintains higher cell proliferation rate in PKD cells compared with control cells. PKD cells also displayed increased lactate formation and extracellular acidification indicative of aerobic glycolysis (Warburg effect), which was blocked by ADAM17 inhibition. We propose that ADAM17 is a key promoter of cellular proliferation in PKD cells by activating the EGFR/ERK axis and a proproliferative glycolytic phenotype.
Quick Links:
 
Quick Links:
 

Expression

Publication --> Expression annotations

 

Other

7 Bio Entities

Trail: Publication

0 Expression