Hormonal Regulation

of Epithelial Ion Transport and Proliferation

Brian Harvey

Department of Molecular Medicine

Royal College of Surgeons in Ireland

www.rcsi.ie/molmed/

Irish EpiPhys Meeting

Kilkenny 2009

Estrogen - regulation of epithelial ion transport

Estrogen - COX & PLA2 signaling in breast cancer

Estrogen - anti-proliferative protection in malignant mesothelioma

Estrogen - KCNQ1 and Wnt signaling in colorectal cancer

Estrogen – lung immune and ASL responses in Cystic Fibrosis ‘gender gap’

Aldosterone – renal ENaC sub-cellular trafficking

Aldosterone – renal Cell Proliferation (polycystic kidney disease)

Lipoxin A4 – lung Airway Surface Liquid, Ciliary Beat in CF & Asthma

Projects

O’Mahony et al. Mol Endo 2009

Estrogen regulation of the KCNQ1 channel

Estrogen and Fluid Retention

O’Mahony & Harvey J Physiol 2009

Na+

Blood Ultra-filtrate

H2OSalt conservation

Hypertension ENaC

Aldosterone and the Epithelial Sodium Channel

MR

Aldosterone

SGK Nedd4,2

P

U

Kidney collecting duct

Activation of PKD by Aldosterone: A new paradigm of ENaC regulation

SRE

SGK

SrcHSP84

Aldo

PKC

PKD

PKC

Trafficking

Aldo

MR HSP84

P

AldoMR

Aldo

MR

ENaC

Stability

Expression