Human RELMbeta is a mitogenic factor in lung cells and induced in hypoxia.
RELMbeta (resistin-like molecule) represents the most related human homologue of mouse RELMalpha, also known as hypoxic-induced mitogenic factor (HIMF). In this study, we isolated RELMbeta cDNA from human lung tissue and performed regulatory and functional expression studies. RELMbeta mRNA was upregulated in hypoxia in human lung A549 cell line as well as primary cultured adventitial fibroblasts and smooth muscle cells (SMC) of pulmonary arteries. Upon transfection of a RELMbeta encoding expression plasmid into these cells, we observed significant induction of proliferation particularly in SMC and A549 cells, which could be blocked by phosphatidyl-inositol 3-kinase (PI3K) inhibitors LY294002 and wortmannin. The results suggest that human RELMbeta may contribute to hypoxic-induced pulmonary vascular remodeling processes or hypoxia related fibrotic lung disease.
Renigunta
Aparna
A
University of Giessen Lung Center (UGLC), Medical Clinic II, Biochemistry, Friedrichstr. 24, Justus-Liebig University, D-35392 Giessen, Germany.
Hild
Christiane
C
Rose
Frank
F
Klepetko
Walter
W
Grimminger
Friedrich
F
Seeger
Werner
W
Hänze
Jörg
J
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D015687:Cell Hypoxia; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D003238:Connective Tissue / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D020932:Nerve Growth Factor / Q000096:biosynthesis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011506:Proteins; D011651:Pulmonary Artery / Q000378:metabolism / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000378:metabolism / Q000473:pathology; D017386:Sequence Homology, Amino Acid; D000077191:Wortmannin
D000730:Androstadienes; D002867:Chromones; D036341:Intercellular Signaling Peptides and Proteins; D009025:Morpholines; D020932:Nerve Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D011506:Proteins; D000077191:Wortmannin; C486574:RETNLB protein, human; C413576:Retnla protein, mouse; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one