Table of Contents
Journal of Allergy
Volume 2013 (2013), Article ID 740973, 11 pages
http://dx.doi.org/10.1155/2013/740973
Research Article

Increased Expression of RhoA in Epithelium and Smooth Muscle of Obese Mouse Models: Implications for Isoprenoid Control of Airway Smooth Muscle and Fibroblasts

1Departments of Pediatrics, Case Western Reserve University and Rainbow Babies and Children’s Hospital, 10900 Euclid Avenue, Cleveland, OH 44106-4948, USA
2Frances Payne Bolton School of Nursing, Case Western Reserve University, 8th Floor BRB, 10900 Euclid Avenue, Cleveland, OH 44106-4948, USA
3Department of Genetics and Genome Sciences, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4948, USA
4Department of Pharmacology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4948, USA

Received 8 February 2013; Revised 22 April 2013; Accepted 21 May 2013

Academic Editor: Balram Ghosh

Copyright © 2013 Kristie R. Ross et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The simultaneous rise in the prevalence of asthma and obesity has prompted epidemiologic studies that establish obesity as a risk factor for asthma. The alterations in cell signaling that explain this link are not well understood and warrant investigation so that therapies that target this asthma phenotype can be developed. We identified a significant increase in expression of the small GTPase RhoA in nasal epithelial cells and tracheal smooth muscle cells from leptin-deficient (ob/ob) mice compared to their wild-type counterparts. Since RhoA function is dependent on isoprenoid modification, we sought to determine the role of isoprenoid-mediated signaling in regulating the viability and proliferation of human airway smooth muscle cells (ASM) and normal human lung fibroblasts (NHLF). Inhibiting isoprenoid signaling with mevastatin significantly decreased the viability of ASM and NHLF. This inhibition was reversed by geranylgeranyl pyrophosphate (GGPP), but not farnesyl pyrophosphate (FPP), suggesting specificity to the Rho GTPases. Conversely, increasing isoprenoid synthesis significantly increased ASM proliferation and RhoA protein expression. RhoA expression is inherently increased in airway tissue from ob/ob mice, and obesity-entrained alterations in this pathway may make it a novel therapeutic target for treating airway disease in the obese population.