Bruce D. Uhal

        uhal@msu.edu
        Phone: (517) 355-6475 ext. 1249
        Home Department: Physiology
        Home Page: Physiology

Professor, Physiology; Ph. D., Saint Louis University 1987

My laboratory has been studying the stem cell function of lung alveolar epithelial type II cells and its regulation in the pathogenesis of pulmonary fibrosis through the use of experimental animal models and lung cell culture systems. Recently we discovered that during lung injury, type II cells and adjacent lung fibroblasts begin synthesizing the vasoactive peptide angiotensin II, independently of the “endocrine” renin-angiotensin system that functions within the vasculature to control blood pressure. More importantly, we found that locally-synthesized angiotensin II is a key regulator of apoptosis (cell suicide), and that blockade of angiotensin function can both ameliorate the apoptosis of alveolar epithelial cells and prevent the lung fibrosis that follows a variety of lung injuries. Our current work is focused on defining the factors that induce the expression of the gene for angiotensinogen, the precursor of angiotensin II, within the alveolar epithelium. We also are beginning to identify the epithelial-specific converting enzymes and receptor signaling pathways responsible for the local generation of angiotensin and its ability to induce apoptosis in response to pathophysiological stimuli. The information gained from these studies will ultimately provide a foundation from which to design new strategies for preventing epithelial cell death and for blocking the injuries that lead to lung disease.

Selected Publications

Wang, R., G. Alam, A. Zagariya, C. Gidea, H. Pinillos, O. Lalude, G. Choudhary and B.D. Uhal. 2000. Apoptosis of lung epithelial cells in response to TNF-alpha requires angiotensin II generation de novo. J. Cell. Physiol.185:253-259. 

Fine, A., Y. Janssen-Heininger, R. P. Soultanakis, S. Swisher and B. D. Uhal. 2000. Apoptosis in Lung Pathophysiology.  Am. J. Physiol:Lung, 279(3):L423-L427. 

Wang, R., O. Ibarra-Sunga, R. Pick and B. D. Uhal. 2000. Abrogation of bleomycin-induced epithelial apoptosis and lung fibrosis by captopril or by a caspase inhibitor. Am. J. Physiol.:Lung 279:L143-L151.