title: Role of MCPIP1 in the Endothelial-Mesenchymal Transition Induced by Silica.
abstract: BACKGROUND
  Silicosis is characterized by the accumulation of fibroblasts and the excessive deposition of extracellular matrix. Fibroblast generation via endothelial-mesenchymal transition (EndMT) is one process responsible for this accumulation of fibroblasts. However, the mechanisms underlying EndMT remain unknown.
  
  
  METHODS
  Human umbilical vein endothelial cells (HUVECs) were exposed to SiO2 (50 µg/cm2). Specific endothelial and mesenchymal markers were evaluated using immunofluorescence and western blot analysis. Functional changes were evaluated by analyzing cell migration and proliferation. LC3-adenovirus transfections were performed, and changes in autophagy were measured using a marker of autophagy.
  
  
  RESULTS
  SiO2 induced decreases in the endothelial cell-specific markers in HUVECs while dramatically increasing mesenchymal cell product levels and mesenchymal functions. Although MCPIP1 expression increased in parallel with the increase in specific mesenchymal cell products, the MCPIP1 expression level was not consistent with the observed decrease in specific endothelial marker expression. Autophagy mediated the effects of MCPIP1, as rapamycin and 3-MA enhanced and attenuated the effect of SiO2 on HUVECs, respectively. MAPKs and the PI3K/Akt pathway were involved in the regulation of MCPIP1 by SiO2, and Pyk2 and MLC-2 mediated cell migration.
  
  
  CONCLUSIONS
  Our findings reveal a new potential function of MCPIP1, suggesting a possible mechanism of fibrosis in pulmonary silicosis.
authors.affiliation: Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chao
authors.forename: Xingang
authors.initials: X
authors.lastname: Wang
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Zhang
authors.forename: Tiebing
authors.initials: T
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Zewei
authors.initials: Z
authors.lastname: Zhou
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.forename: Yusi
authors.initials: Y
authors.lastname: Cheng
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Tu
authors.forename: Honghong
authors.initials: H
authors.lastname: Yao
mesh_terms: D001343:Autophagy / Q000187:drug effects; D024722:Cardiac Myosins / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008648:Mesoderm / Q000187:drug effects / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism; D010641:Phenotype; D010766:Phosphorylation / Q000187:drug effects; D012260:Ribonucleases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D012822:Silicon Dioxide / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D018994:Myosin Light Chains; D014157:Transcription Factors; C107184:myosin light chain 2; D012822:Silicon Dioxide; D051418:Focal Adhesion Kinase 2; D012260:Ribonucleases; C510646:ZC3H12A protein, human; D024722:Cardiac Myosins