title: Control of collagen deposition in mammalian lung.
abstract: This review considers the mechanisms controlling collagen deposition in mammalian lung in five different states: normal development, fibrosis, erosion, pneumonectomy, and the steady state. Deposition is the net result of positive and negative processes. The major positive processes are control of cell number and type, regulation of transcription and translation, post-translational modifications, fibril formation, and covalent cross-linking. The negative mechanisms are intracellular degradation, collagenase-mediated degradation, and phagocytosis, and they are integral to the life cycle of collagen. Cytokines and growth factors have many and complex effects on all the processes that constitute collagen metabolism. Interleukin-1 and tumor necrosis factor-alpha can either stimulate or inhibit collagen accumulation, presumably depending on the immediate environment. Interleukin-6 inhibits collagen degradation, and gamma-interferon inhibits collagen production. Platelet derived growth factor and fibroblast growth factor have powerful mitogenic effects on connective tissue cells in lung, and can also affect collagen production directly. Transforming growth factor-beta activates a battery of processes that uniformly contribute to accumulation of collagen. Transforming growth factor-beta may be the "master switch" for a fibrotic program in lung. Therapeutic approaches to controlling lung fibrosis by manipulating cytokine levels are promising. Prostaglandin E has uniformly negative effects on net collagen accumulation and may play a central role in an erosion program.
authors.affiliation: Pediatric Research Center, Schneider Children's Hospital, Long Island Jewish Medical Center, New Hyde Park, New York 11040, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Bienkowski
authors.forename: M G
authors.initials: MG
authors.lastname: Gotkin
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000601:surgery; D008322:Mammals; D011453:Prostaglandins / Q000502:physiology; D011658:Pulmonary Fibrosis / Q000378:metabolism
chemical_list: D016207:Cytokines; D011453:Prostaglandins; D003094:Collagen