title: The role of MIF, cyclinD1 and ERK in the development of pulmonary hypertension in broilers.
abstract: Pulmonary hypertension (PH) is a major disease in the broiler breeding industry. During PH, the pulmonary artery undergoes remodelling, which is caused by pulmonary vascular smooth muscle cell proliferation. CyclinD1 regulates cell proliferation. This study investigated the role of cyclinD1 in the development of PH in broilers, and which bioactivators and signalling pathway are involved in the pathological process. The PH group contained 3-4-week-old broilers with clinical PH, and the healthy group broilers from the same flock without PH. Histopathology indicated pulmonary arterial walls were thicker in the PH group compared with the healthy group. Target gene expressions of macrophage migration inhibitory factor (MIF), extracellular signal-regulated kinase (ERK), and cyclinD1 detected by quantitative real-time PCR were upregulated in the PH group compared with the healthy group. Immunohistochemistry showed MIF, phosphorylated ERK (p-ERK) and cyclinD1 were present on pulmonary vascular walls; MIF was present in the cytoplasm of arterial endothelial cells and smooth muscle cells; p-ERK and cyclinD1 were present in smooth muscle cell cytoplasm. Western blotting demonstrated that MIF, p-ERKand cyclinD1 levels were significantly higher (P < 0.01) in the PH group compared with the healthy group. In summary, increased MIF in PH broiler pulmonary arteries upregulated cyclinD1 via the ERK signalling pathway to induce pulmonary vascular smooth muscle cell proliferation, causing pulmonary artery remodelling and hypertension.
authors.affiliation: a College of Animal Science and Technology , Shanxi Agricultural University , Taigu , People's Republic of China.
authors.forename: Haoyun
authors.initials: H
authors.lastname: Li
authors.affiliation: a College of Animal Science and Technology , Shanxi Agricultural University , Taigu , People's Republic of China.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: a College of Animal Science and Technology , Shanxi Agricultural University , Taigu , People's Republic of China.
authors.forename: Lingli
authors.initials: L
authors.lastname: Chen
authors.affiliation: a College of Animal Science and Technology , Shanxi Agricultural University , Taigu , People's Republic of China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Han
authors.affiliation: a College of Animal Science and Technology , Shanxi Agricultural University , Taigu , People's Republic of China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Li
authors.affiliation: a College of Animal Science and Technology , Shanxi Agricultural University , Taigu , People's Republic of China.
authors.forename: Han
authors.initials: H
authors.lastname: He
authors.affiliation: a College of Animal Science and Technology , Shanxi Agricultural University , Taigu , People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: a College of Animal Science and Technology , Shanxi Agricultural University , Taigu , People's Republic of China.
authors.forename: Nan
authors.initials: N
authors.lastname: Huang
authors.affiliation: a College of Animal Science and Technology , Shanxi Agricultural University , Taigu , People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Ren
authors.affiliation: a College of Animal Science and Technology , Shanxi Agricultural University , Taigu , People's Republic of China.
authors.forename: Fangying
authors.initials: F
authors.lastname: Pei
authors.affiliation: a College of Animal Science and Technology , Shanxi Agricultural University , Taigu , People's Republic of China.
authors.forename: Guilan
authors.initials: G
authors.lastname: Li
authors.affiliation: a College of Animal Science and Technology , Shanxi Agricultural University , Taigu , People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Cheng
authors.affiliation: a College of Animal Science and Technology , Shanxi Agricultural University , Taigu , People's Republic of China.
authors.forename: Wenkui
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002645:Chickens; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006976:Hypertension, Pulmonary / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D011651:Pulmonary Artery / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation; D066253:Vascular Remodeling
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D019938:Cyclin D1; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Broiler; MIF; cyclinD1; p-ERK/ERK; pulmonary hypertension