The family of 14-3-3 proteins and specifically 14-3-3? are up-regulated during the development of renal pathologies.

ABSTRACT: Chronic kidney disease, the end result of most renal and some systemic diseases, is a common condition where renal function is compromised due to fibrosis. During renal fibrosis, calreticulin, a multifunctional chaperone of the endoplasmic reticulum (ER) is up-regulated in tubular epithelial cells (TECs) both in vitro and in vivo. Proteomic analysis of cultured TECs overexpressing calreticulin led to the identification of the family of 14-3-3 proteins as key proteins overexpressed as well. Furthermore, an increased expression in the majority of 14-3-3 family members was observed in 3 different animal models of renal pathologies: the unilateral ureteric obstruction, the nephrotoxic serum administration and the ischaemia-reperfusion. In all these models, the 14-3-3? isoform (also known as stratifin) was predominantly overexpressed. As in all these models ischaemia is a common denominator, we showed that the ischaemia-induced transcription factor HIF1? is specifically associated with the promoter region of the 14-3-3? gene. Finally, we evaluated the expression of the family of 14-3-3 proteins and specifically 14-3-3? in biopsies from IgA nephropathy and membranous nephropathy patients. These results propose an involvement of 14-3-3? in renal pathology and provide evidence for the first time that hypoxia may be responsible for its altered expression.

SUBMITTER: Rizou M 

PROVIDER: S-EPMC6111864 | biostudies-other | 2018 Sep

REPOSITORIES: biostudies-other