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. Conclusion: Our findings reveal a new potential function of MCPIP1, suggesting a possible mechanism of fibrosis in pulmonary silicosis.

Low-Intensity Pulsed Ultrasound Prevents the Oxidative Stress Induced Endothelial-Mesenchymal Transition in Human Aortic Endothelial Cells

“…It is known that EndMT relies critically on the capacity of cell migration [12, 26]. In order to investigate whether such a property contributes to the beneficial effects of LIPUS, we examined cell migration by wound healing and transwell assays.…”

circRNA Mediates Silica-Induced Macrophage Activation Via HECTD1/ZC3H12A-Dependent Ubiquitination

“…Cells were transfected with a lentivirus (HANBIO Inc., Shanghai, China) using a previously described method 15 , 16 .…”

Exosomes from high glucose-treated glomerular endothelial cells trigger the epithelial-mesenchymal transition and dysfunction of podocytes

“…Endothelial cells undergoing the EndoMT can synthesize and secrete fibrogenic/inflammatory cytokines and produce excess ECM in fibrotic lesions, contributing to the development and progression of fibrosis in the lungs, liver, heart, dermis, cornea and kidneys 32 . Previous reports mention that some harmful stimulating factors, such as TGF-β1 33 , CTGF 34 , SiO 2 35 , serum response factor 36 , hypoxia 37 , can induce an EndoMT-like phenotype. In addition, recent research shows that under pathological conditions, cells undergoing the EndoMT can activate the transdifferentiation of neighboring cells via secretion of profibrotic cytokines in a paracrine-dependent manner 38 .…”