title: The antifibrosis effect of adrenomedullin in human lung fibroblasts.
abstract: Adrenomedullin (AM) is a regulatory peptide involved in cellular proliferation and protein synthesis. The authors investigated AM and the AM receptor system in the human fetal lung fibroblasts (HFLFs), and assessed whether AM can inhibit proliferation and collagen synthesis in HFLFs under hypoxia. Fibroblasts were exposed to hypoxia (2% O(2)) after the addition of AM. The effects of AM and transforming growth factor β1 (TGF-β1) on the proliferation of fibroblasts were determined by the methanethiosulfonate (MTS) assay. Total collagen synthesis was determined by [(3)H]proline incorporation. TGF-β1 levels in the culture supernatant were measured by enzyme-linked immunosorbent assay (ELISA). The concentration of intracellular calciumion ([Ca(2+)](i)) in fibroblasts was detected with a laser scanning confocal microscope. AM, adrenomedullin receptor (ADMR), calcitonin receptor-like receptor (CRLR), AM receptor chaperone receptor activity-modifying protein-1 (RAMP1),RAMP2, and RAMP3 were detected in the HFLFs. The hypoxia-induced increases in cell proliferation, collagen synthesis, and TGF-β1 production were inhibited by AM. AM also inhibited proliferation and collagen synthesis in fibroblasts induced by TGF-β1. AM caused a decrease of the hypoxia-induced [Ca(2+)](i) in fibroblasts. This study suggests that AM is produced by HFLFs and AM may function as an antifibrosis factor that protects cells from hypoxic pulmonary damage through its receptors.
authors.affiliation: Department of Respiratory Disease, Military General Hospital of Beijing PLA, Beijing, China.
authors.forename: Shu-Ling
authors.initials: SL
authors.lastname: Hao
authors.forename: Zhong-He
authors.initials: ZH
authors.lastname: Yu
authors.forename: Bao-Shen
authors.initials: BS
authors.lastname: Qi
authors.forename: Ji-Zheng
authors.initials: JZ
authors.lastname: Luo
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Wang
mesh_terms: D053607:Adrenomedullin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D058286:Calcitonin Receptor-Like Protein / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D048708:Cell Growth Processes / Q000502:physiology; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D003094:Collagen / Q000096:biosynthesis / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D058261:Receptor Activity-Modifying Proteins / Q000378:metabolism; D058265:Receptors, Adrenomedullin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D058286:Calcitonin Receptor-Like Protein; D058261:Receptor Activity-Modifying Proteins; D058265:Receptors, Adrenomedullin; D053773:Transforming Growth Factor beta1; D053607:Adrenomedullin; D003094:Collagen; D002118:Calcium