GADD45a promoter regulation by a functional genetic variant associated with acute lung injury.

ABSTRACT:

Rationale

Growth arrest DNA damage inducible alpha (GADD45a) is a stress-induced gene we have shown to participate in the pathophysiology of ventilator-induced lung injury (VILI) via regulation of mechanical stress-induced Akt ubiquitination and phosphorylation. The regulation of GADD45a expression by mechanical stress and its relationship with acute lung injury (ALI) susceptibility and severity, however, remains unknown.

Objectives

We examined mechanical stress-dependent regulatory elements (MSRE) in the GADD45a promoter and the contribution of promoter polymorphisms in GADD45a expression and ALI susceptibility.

Methods and results

Initial studies in GADD45a knockout and heterozygous mice confirmed the relationship of GADD45a gene dose to VILI severity. Human lung en

SUBMITTER: Mitra S 

PROVIDER: S-EPMC4062486 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature