ABSTRACT
Semaphorin 4A plays a regulatory role in immune function and angiogenesis. However, its specific involvement in controlling lung fibrosis, a process that is closely related to angiogenesis and inflammation is still poorly understood. In the present study, we show that treatment of Sema4A on normal lung fibroblasts induces expression of proteins that contribute to a contractile phenotype, including alpha-smooth muscle actin (alpha-SMA), ezrin, moesin, and paxillin. We confirm that Sema4A enhances the ability of lung fibroblasts to contract collagen gel. Sema4A treatment led to resistance to apoptosis in normal lung fibroblasts. Relative to normal lung fibroblasts, fibroblasts cultured from scars of patients with the fibrotic disease Systemic Sclerosis (SSc) showed elevated Sema4A secretion, enhanced alpha-SMA, ezrin, moesin, and paxillin expression, and high ability to induce collagen gel contraction. Using neutralizing antibody against Sema4A receptor, PlexinD1, we found that endogenous Sema4A signalling in SSc fibroblast was through PlexinD1 receptor. We then identified the signalling mechanism through which Sema4A-PlexinD1 promotes the ability of normal fibroblasts to contract a collagen gel matrix. Western blot analysis showed that Sema4A activated the Akt pathway in lung fibroblasts, and the specific inhibitor of Akt pathway, Akt inhibitor III, blocked the ability of Sema4A to promote the ability of lung fibroblasts to contract a collagen gel matrix. Thus, blocking Sema4APlexinD1- Akt cascades might be beneficial in reducing pulmonary fibrosis.
Subject(s)
Cell Adhesion Molecules, Neuronal/metabolism , Fibroblasts/metabolism , Lung/pathology , Proto-Oncogene Proteins c-akt/metabolism , Semaphorins/metabolism , Apoptosis/drug effects , Cells, Cultured , Collagen/metabolism , Fibroblasts/drug effects , Fibrosis/metabolism , Fibrosis/pathology , Humans , Intracellular Signaling Peptides and Proteins , Lung/metabolism , Membrane Glycoproteins , Scleroderma, Systemic/pathology , Semaphorins/genetics , Semaphorins/pharmacology , Signal TransductionABSTRACT
Statistics of the structure of educational level and worked years of 140 occupied nurses, analysed by ABC curvegram, showed that the key training objects are class A (1 to 10 years at work) and class B nurses. Then the goal of nurses' training at work during 3 years for class A and B was made according to the difference of their classes and need of knowledge. In order to improve the effect of 3.3 style nurse training goal a method of two-direction teaching and assessing were applied, actual effect was achieved during a three-year conduction.