Mice lacking uteroglobin are highly susceptible to developing pulmonary fibrosis.
Uteroglobin (UG) is an anti-inflammatory protein secreted by the airway epithelia of all mammals. UG-knockout (UG-KO) mice sporadically develop focal pulmonary fibrosis (PF), a group of complex interstitial disorders of the lung that has high mortality and morbidity; however, the molecular mechanism(s) remains unclear. We report here that UG-KO mice are extraordinarily sensitive to bleomycin, an anti-cancer agent known to induce PF and readily develop PF when treated with an extremely low dose of bleomycin that has virtually no effect on the wild type littermates. We further demonstrate that UG prevents PF suppressing bleomycin-induced production of pro-inflammatory T-helper 2 cytokines and TGF-beta, which are also pro-fibrotic. Our results define a critical role of UG in preventing the development of PF and provide the proof of principle that recombinant UG may have therapeutic potential.
Lee
Yi-Ching
YC
Section on Developmental Genetics, Heritable Disorders Branch, National Institute of Child Health and Human Development, The National Institutes of Health, Building 10, Rm 9D42, 10, Center Drive, Bethesda, MD 20892-1830, USA.
Zhang
Zhongjian
Z
Mukherjee
Anil B
AB
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001761:Bleomycin; D016207:Cytokines / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011014:Pneumonia / Q000139:chemically induced; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D016019:Survival Analysis; D018418:Th2 Cells / Q000276:immunology; D014598:Uteroglobin / Q000235:genetics / Q000502:physiology*
D015415:Biomarkers; D016207:Cytokines; D001761:Bleomycin; D014598:Uteroglobin