Thrombospondin‐1 and microRNA‐1 expression in response to multiwalled carbon nanotubes in alveolar epithelial cells

Abstract

Thrombospondin-1 (TSP-1) is a glycoprotein that plays a role in extracellular matrix (ECM) remodeling. Previously, we have shown that multi-walled carbon nanotubes (MWCNT) regulate ECM components TGFβ and its target Col3A1 in alveolar epithelial cells. In the present study, we investigated the effect of MWCNT on TSP-1 and microRNA-1 (miR-1) in the regulation of TGFβ in ECM remodeling using alveolar epithelial A549 cells. A549 cells were treated with MWCNT (20 or 50 µg/ml) for 6 or 24 h and the expression of TSP-1 and miR-1, and the exogenous miR-1 effect on cell morphology were analyzed. MWCNT induced in a time- and dose-dependent manner the expression of TSP-1. miR-1 was suppressed by MWCNT after 6 or 24 h of treatment regardless of the dose. TSP-1 and miR-1 negatively correlated with each other, r = −0.58. Exogenous administration of miR-1 induced alveolar epithelial cell morphology changes including cell clustering, whereas inhibition of miR-1 induced less cell to cell contact, cell rounding, and cellular projections. IntAct molecular network interactions analysis revealed that TSP-1 interacts with 21 molecular factors including ECM genes, and molecules. These results indicate a relationship between that TSP-1, MWCNT and TGFβ, and suggest TSP-1 may play a role in MWCNT-induced TGFβ and ECM remodeling. Moreover, these data also suggest an inverse relationship between TSP-1 and miR-1 and a potential role of miR-1 in MWCNT-induced fibrotic signaling.

miR221 regulates cell migration by targeting annexin a1 expression in human mesothelial MeT-5A cells neoplastic-like transformed by multi-walled carbon nanotube

“…MiRNAs (miR122/206/130/210) in the blood were significantly up- or down-regulated in mice with pathological alteration in the lung after methylcholanthrene administration followed by MWCNT inhalation [ 34 ]. MiR1 was suppressed by MWCNT after 6 or 24 h of treatment regardless of the dosage in alveolar epithelial A549 cells, and exogenous administration of miR1 induced cell morphology changes including cell clustering, whereas inhibition of miR1 induced less cell to cell contact, cell rounding, and cellular projections [ 35 ].…”

Idiopathic Pulmonary Comorbidities and Mechanisms

“…TGF β in complex with TSP-1 is biologically active and favors TGF β binding to cell receptors [ 101 ]. Platelets, endothelial cells, smooth muscle cells, neutrophils, monocytes, macrophages, alveolar macrophages, fibroblasts, and epithelial cells all produce TSP-1 [ 102 – 106 ]. TSP-1 regulates multiples cellular processes such as cell migration, cell adhesion, cell proliferation, apoptosis, coagulation, wound repair, and fibrosis [ 107 , 108 ].…”

MicroRNA‐17‐5p restrains the dysfunction of Ang‐II induced podocytes by suppressing secreted modular calcium‐binding protein 2 via NF‐κB and TGFβ signaling

“…MicroRNAs (miRNAs) are small endogenous RNAs that modulate gene‐expression post‐transcriptionally 14‐16 . Over the past decades, miRNAs have been confirmed to serve as important biomarkers for the treatment of renal diseases 17‐19 .…”

“…[11][12][13] MicroRNAs (miRNAs) are small endogenous RNAs that modulate gene-expression post-transcriptionally. [14][15][16] Over the past decades, miRNAs have been confirmed to serve as important biomarkers for the treatment of renal diseases. [17][18][19] Importantly, it has reported that miRNAs are promising biomarkers for the diagnosis and prognosis of glomerulonephritis.…”