Effect of Chronic Hypoxia on Proliferation, Apoptosis, and HSP70 Expression in Mouse Bronchiolar Epithelial Cells

E-K. KIM, J.D. PARK, S-Y. SHIM, H-S. KIM, B.I. KIM, J-H. CHOI, J.E. KIM¹

Department of Pediatrics, 1Department of Pathology, Seoul National University College of Medicine, Seoul, Korea

Received February 22, 2005
Accepted August 10, 2005
On-line available October 17, 2005

Summary
Heat shock proteins (HSPs) can be induced by various stresses and play an important role in cell cycle progression. HSP70 has been shown to act as an inhibitor of apoptosis. We studied HSP70 expression in bronchial epithelial cells of C57BL/6 mice and homozygous HPS70 knockout mice (hsp70.1–/–) exposed to chronic hypoxic stress. We also investigated changes in cellular proliferation and apoptosis in relation to HSP70. Lungs were removed from mice after a three-week period of exposure to 10 % O2. Immunoblots for HSP70 and immunohistochemical staining for HSP70 and Ki-67 were performed. Apoptosis was assessed using the TUNEL assay. The three-week period of hypoxic stress did not change HSP70 levels in total lung tissue, but a significant reduction in HSP70 expression was observed in bronchiolar epithelial cells. In wild type mice, both HSP70 and Ki-67 expression were significantly reduced in bronchiolar epithelial cells. In homozygous HPS70 knockout mice (hsp70.1–/–), apoptosis of bronchiolar epithelial cells was significantly increased. Our results suggest that HSP70 may exert anti-apoptotic effects in mouse bronchiolar epithelial cells.


Key words
Chronic hypoxia • Bronchiolar epithelium • HSP70 • Proliferation • Apoptosis