The Expression And Distribution Of MIF,p-ERK And CyclinD1 In The Lung Of Broilers With Pulmonary Hypertension

[Purpose] Pulmonary hypertension (PH) is one of major diseases in the broiler breeding industry. A significant tache in the development of PH is the remodeling of pulmonary artery, which gives priority to the proliferation of pulmonary vascular smooth muscle cells(PVSMCs). CyclinDl is a key factor in the regulation of cell proliferation, and if this factor is involved in the PVSMCs proliferation of broilers with PH has not been reported. Therefore, we conducted this study. According to the reports, extracellular signal-regulated kinase (ERK) is the major signal pathway to regulate the expression of cyclinD1. In addition, our previous work has shown that the expression of macrophage migration inhibition factor (MIF) in broiler lungs with pulmonary hypertension is significantly higher than those in healthy broilers, which means that MIF has involved in the development of PH in broilers. This experiment is aiming to clarify the relationship among these three proteins on the pathogenesis of PH in broiler, which is to say whether MIF could induce pulmonary artery wall thickening by activating ERK1/2 pathway to upregulate the expression of cyclinD1 and thereby promoting the PVSMCs proliferation.[Methods] The PH group was about 30 day-old broilers with clinical pulmonary hypertension, while the normal was healthy broilers at the same age. The difference of lung vascular morphology between PH group and healthy group was observed by HE staining. The location and expression of MIF, p-ERK and cyclinD1 proteins were detected by Immunohisto-chemistry and western-blotting, and the results between two groups was compared.[Results] The results of HE staining showed that the structure of normal lung could be observed clearly and completely, without leakage and inflammatory cell infiltration. Compared with normal group, the PH group showed arterial intima and media thickening, luminal narrowing and more pulmonary inflammatory cell infiltration around pulmonary vascular observed.The results of Immunohistochemistry showed that positive reaction of MIF, p-ERK and cyclinD1 was observed on the pulmonary vascular walls, in which the expression of MIF located in the cytoplasm of vascular endothelial cells and smooth muscle cells; p-ERK and cyclinD1 located in the cytoplasm of vascular smooth muscle cells.The results of Western-blotting showed that compared with the normal group, the expression of MIF and cyclinD1 in PH group increased significantly (P<0.01), and the phosphorylation of ERK (p-ERK) was significantly upregulated (P<0.01), which indicated ERK pathway was highly activated.[Conclusion] The pulmonary artery media membrane thickening appeared during the development of PH in broilers, which might be related to the increased expression of MIF in lungs, ERK signaling pathway highly activated, and upregulation of cyclinD1.