Human RELMbeta is a mitogenic factor in lung cells and induced in hypoxia |
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Authors: | Renigunta Aparna Hild Christiane Rose Frank Klepetko Walter Grimminger Friedrich Seeger Werner Hänze Jörg |
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Affiliation: | University of Giessen Lung Center (UGLC), Medical Clinic II, Biochemistry, Friedrichstr. 24, Justus-Liebig University, D-35392 Giessen, Germany. |
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Abstract: | 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. |
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Keywords: | RELM, resistin like molecule HIMF, hypoxic-induced mitogenic factor FIZZ, protein found in inflammatory zone SMC, smooth muscle cells FB, fibroblast |
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