title: Fibrocytes are not an essential source of type I collagen during lung fibrosis.
abstract: Progressive fibrosis involves accumulation of activated collagen-producing mesenchymal cells. Fibrocytes are hematopoietic-derived cells with mesenchymal features that potentially have a unique and critical function during fibrosis. Fibrocytes have been proposed as an important direct contributor of type I collagen deposition during fibrosis based largely on fate-mapping studies. To determine the functional contribution of hematopoietic cell-derived type I collagen to fibrogenesis, we use a double-transgenic system to specifically delete the type I collagen gene across a broad population of hematopoietic cells. These mice develop a robust fibrotic response similar to littermate genotype control mice injured with bleomycin indicating that fibrocytes are not a necessary source of type I collagen. Using collagen-promoter GFP mice, we find that fibrocytes express type I collagen. However, fibrocytes with confirmed deletion of the type I collagen gene have readily detectable intracellular type I collagen indicating that uptake of collagen from neighboring cells account for much of the fibrocyte collagen. Collectively, these results clarify several seemingly conflicting reports regarding the direct contribution of fibrocytes to collagen deposition.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109; and.
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Kleaveland
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109; and.
authors.forename: Miranda
authors.initials: M
authors.lastname: Velikoff
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109; and.
authors.forename: Jibing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109; and.
authors.forename: Manisha
authors.initials: M
authors.lastname: Agarwal
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rippe
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109; and.
authors.forename: Bethany B
authors.identifier: http://orcid.org/0000-0003-3051-745X
authors.initials: BB
authors.lastname: Moore
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109; and kevkim@med.umich.edu.
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Kim
mesh_terms: D000818:Animals; D001761:Bleomycin; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D024042:Collagen Type I / Q000172:deficiency* / Q000235:genetics; D015870:Gene Expression; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D021381:Protein Transport; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
chemical_list: D024042:Collagen Type I; D001761:Bleomycin; D049452:Green Fluorescent Proteins