Peroxisome proliferators alter lipid acquisition and elastin gene expression in neonatal rat lung fibroblasts.
During the alveolar stage of lung development, lipid droplet-laden interstitial cells are present at the base of elongating alveolar septa. These cells that have been named lipid interstitial cells or lipofibroblasts (LFs) may supply lipids for surfactant production, the synthesis of membrane phospholipids, and/or energy metabolism. They also have myofibroblastic characteristics and participate in the generation of the interstitial elastic fiber network, that is, in the pulmonary alveolar septum. To understand how this cell regulates its lipid-storing and elastin-producing properties, we have examined the effects of peroxisome proliferators on the expression of the genes that are associated with an elastin-producing myofibroblastic phenotype or an adipocyte-like phenotype. Two known ligands for peroxisome proliferator-activated receptors, 5,8,11,14-eicosatetraynoic acid (ETYA) and 15-deoxy-delta-12,14-prostaglandin J2 (15-dPGJ2), decrease elastin gene transcription and the steady-state levels of tropoelastin (TE) and alpha-smooth muscle actin mRNAs in cultured LFs. Concurrently, cultured LFs increase the expression of adipocyte lipid binding protein, which is regarded as an adipocyte-specific protein, and accumulate lipid droplets. Their abilities to store lipids and express desmin intermediate filaments, alpha-smooth muscle actin, and smooth muscle myosin heavy chain in contractile filaments in vitro illustrate similarities among the pulmonary LF, the hepatic lipocyte, and the contractile interstitial cell, which contribute to the repair reaction in the lung after pulmonary injury.
McGowan
S E
SE
Department of Veterans Affairs Research Service, Iowa City, Iowa, USA.
Jackson
S K
SK
Doro
M M
MM
Olson
P J
PJ
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology*; D000199:Actins / Q000096:biosynthesis; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000096:biosynthesis*; D004549:Elastin / Q000096:biosynthesis*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D050356:Lipid Metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D008830:Microbodies / Q000187:drug effects*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D000199:Actins; D003598:Cytoskeletal Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D015117:5,8,11,14-Eicosatetraynoic Acid; D004549:Elastin; D015230:Prostaglandin D2