The pathophysiological role of prothymosin ? in polycystic kidney disease

  • 陳 怡成

Student thesis: Doctoral Thesis

Abstract

Polycystic kidney disease (PKD) is a genetic disorder characterized by the formation of multiple renal cysts Previous research shows that the transgenic overexpression of prothymosin ? (ProT) induces the development of PKD; however the molecular mechanism underlying the overexpression of ProT in PKD remains unclear Here we elucidate the upstream and downstream molecular mechanism of ProT in PKD We find an inflammation-associated molecule TNF receptor-associated factor 6 (TRAF6) is increased in both the mouse PKD model and in the kidney of patient with PKD TRAF6 is able to enhance the expression of ProT through catalyzing the ubiquitination of ProT and on the other hand the up-regulated ProT induces a global protein acetylation which is accompanied by the acetylation and hyper activation of STAT3 We further used two systems to determine the significance of our study in cyst formation in PKD 1) Administration of TRAF6 inhibitor is able to reduce the expression of ProT in vitro and efficiently slows the growth of renal cyst in PKD 2) We performed a cyst formation assay in vitro to demonstrate that overexpression of ProT induces cyst formation through the activation of STAT3 In summary the detailed pathological mechanism of PKD is not fully understood and there is not yet an effective therapeutic approach In this study we describe the significance of TRAF6 and ProT in PKD thus helping to clarify the molecular mechanisms of cystic physiology and this will knowledge will contribute to developing new therapeutic strategies for PKD
Date of Award2015 Aug 26
Original languageEnglish
SupervisorChao-Liang Wu (Supervisor)

Cite this

The pathophysiological role of prothymosin ? in polycystic kidney disease
怡成, 陳. (Author). 2015 Aug 26

Student thesis: Doctoral Thesis