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Endocrinology Vol. 138, No. 9 3695-3703
Copyright © 1997 by The Endocrine Society

ARTICLES

Peroxisome Proliferator-Activated Receptor {gamma}1 Expression Is Induced during Cyclic Adenosine Monophosphate-Stimulated Differentiation of Alveolar Type II Pneumonocytes1

Laura F. Michael2, Mitchell A. Lazar and Carole R. Mendelson

Departments of Biochemistry and Obstetrics-Gynecology (L.F.M., C.R.M.), The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75235-9038; and Division of Endocrinology, Diabetes and Metabolism, Departments of Medicine and Genetics (M.A.L.), University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6149

Address all correspondence and requests for reprints to: Carole R. Mendelson, Ph.D., Department of Biochemistry, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75235-9038. E-mail: cmende{at}biochem.swmed.edu

The primary function of lung alveolar type II cells is to synthesize pulmonary surfactant, a lipoprotein enriched in dipalmitoylphosphatidylcholine. Because type II pneumonocytes are highly lipogenic, we considered the possible role of the adipogenic nuclear hormone receptor, peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}), in their differentiation from epithelial cell precursors. A degenerate PCR-screening strategy revealed that multiple PPARs, including PPAR{gamma}, are present in differentiated type II cells. A PCR-amplified PPAR{gamma} DNA-binding domain was used to isolate a full-length PPAR{gamma}1 complementary DNA clone from a rabbit type II cell complementary DNA library. Although another PPAR{gamma} isoform, PPAR{gamma}2, is known to be highly expressed in adipocytes, only PPAR{gamma}1 was detected in rabbit type II cells by use of RT-PCR and by library screening. Rabbit PPAR{gamma}1 has 90% nucleotide sequence identity and 95% amino acid identity to mouse PPAR{gamma}1. PPAR{gamma}1 messenger RNA was readily detected in total RNA isolated from rabbit type II pneumonocytes cultured in the presence of cAMP, which causes enlargement of the prealveolar ducts, accelerates the rate of type II cell differentiation, and induces transcription of the major surfactant associated protein, surfactant protein-A. PPAR{gamma}1 messenger RNA also was detected in total RNA isolated from rabbit adipose tissue but not from whole adult or fetal lung, heart, or liver. By Western blot analysis, PPAR{gamma} protein expression was found to occur coincidentally with surfactant protein-A expression during lung type II cell differentiation. In view of the role of PPAR{gamma} in adipocyte differentiation and lipid homeostasis, we postulate that PPAR{gamma}1 induction by cAMP plays a role in the differentiation and expression of lipogenic enzymes in lung type II cells.




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