Peroxisome proliferator-activated receptor γ1 expression is induced during cyclic adenosine monophosphate-stimulated differentiation of alveolar type II pneumonocytes

Laura F. Michael, Mitchell A. Lazar, Carole R. Mendelson

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Abstract

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, peroxiseme proliferator-activated receptor γ (PPARγ), in their differentiation from epithelial cell precursors. A degenerate PCR-screening strategy revealed that multiple PPARs, including PPARγ, are present in differentiated type II cells. A PCR-amplified PPARγ DNA-binding domain was used to isolate a full-length PPARγ1 complimentary DNA clone from a rabbit type II cell complementary DNA library. Although another PPARγ isoform, PPARγ2, is known to be highly expressed in adipocytes, only PPARγ1 was detected in rabbit type II cells by use of RT-PCR and by library screening. Rabbit PPARγ1 has 90% nucleotide sequence identity and 95% amino acid identity to mouse PPARγ1. PPARγ1 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. PPARγ1 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, PPARγ protein expression was found to occur coincidentally with surfactant protein-A expression during lung type II cell differentiation. In view of the role of PPARγ in adipocyte differentiation and lipid homeostasis, we postulate that PPARγ1 induction by cAMP plays a role in the differentiation and expression of lipogenic enzymes in lung type II cells.

Original languageEnglish (US)
Pages (from-to)3695-3703
Number of pages9
JournalEndocrinology
Volume138
Issue number9
DOIs
StatePublished - 1997

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Peroxisome Proliferator-Activated Receptors
Cyclic AMP
Rabbits
Pulmonary Surfactant-Associated Protein A
Lung
Adipocytes
Polymerase Chain Reaction
Cell Differentiation
RNA
Alveolar Epithelial Cells
Pulmonary Surfactants
1,2-Dipalmitoylphosphatidylcholine
Fetal Heart
Messenger RNA
Cytoplasmic and Nuclear Receptors
Gene Library
Surface-Active Agents
Lipoproteins
Adipose Tissue
Protein Isoforms

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

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title = "Peroxisome proliferator-activated receptor γ1 expression is induced during cyclic adenosine monophosphate-stimulated differentiation of alveolar type II pneumonocytes",
abstract = "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, peroxiseme proliferator-activated receptor γ (PPARγ), in their differentiation from epithelial cell precursors. A degenerate PCR-screening strategy revealed that multiple PPARs, including PPARγ, are present in differentiated type II cells. A PCR-amplified PPARγ DNA-binding domain was used to isolate a full-length PPARγ1 complimentary DNA clone from a rabbit type II cell complementary DNA library. Although another PPARγ isoform, PPARγ2, is known to be highly expressed in adipocytes, only PPARγ1 was detected in rabbit type II cells by use of RT-PCR and by library screening. Rabbit PPARγ1 has 90{\%} nucleotide sequence identity and 95{\%} amino acid identity to mouse PPARγ1. PPARγ1 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. PPARγ1 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, PPARγ protein expression was found to occur coincidentally with surfactant protein-A expression during lung type II cell differentiation. In view of the role of PPARγ in adipocyte differentiation and lipid homeostasis, we postulate that PPARγ1 induction by cAMP plays a role in the differentiation and expression of lipogenic enzymes in lung type II cells.",
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N2 - 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, peroxiseme proliferator-activated receptor γ (PPARγ), in their differentiation from epithelial cell precursors. A degenerate PCR-screening strategy revealed that multiple PPARs, including PPARγ, are present in differentiated type II cells. A PCR-amplified PPARγ DNA-binding domain was used to isolate a full-length PPARγ1 complimentary DNA clone from a rabbit type II cell complementary DNA library. Although another PPARγ isoform, PPARγ2, is known to be highly expressed in adipocytes, only PPARγ1 was detected in rabbit type II cells by use of RT-PCR and by library screening. Rabbit PPARγ1 has 90% nucleotide sequence identity and 95% amino acid identity to mouse PPARγ1. PPARγ1 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. PPARγ1 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, PPARγ protein expression was found to occur coincidentally with surfactant protein-A expression during lung type II cell differentiation. In view of the role of PPARγ in adipocyte differentiation and lipid homeostasis, we postulate that PPARγ1 induction by cAMP plays a role in the differentiation and expression of lipogenic enzymes in lung type II cells.

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