MicroRNA-26a promotes epithelial mesenchymal transition in pleural mesothelial cells

Najmunnisa Nasreen, Bhagyalaxmi Sukka-Ganesh, Judith A. Johnson, Ruxana T. Sadikot, Steven A. Sahn, Kamal A. Mohammed

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Pleural space is lined with a dynamic monolayer of cells, the Pleural Mesothelial Cells (PMCs). Pleural inflammation/injury often leads to the development of pleural fibrosis. Pleural fibrosis is characterized by the formation of sub-pleural foci of myofibroblasts that contribute to the exuberant pleural fibrosis. Emerging evidence indicate that microRNA-26a (miR-26a) play a key role in the process of fibrosis. In this study we have determined the role of miR- 26a in PMC Epithelial Mesenchymal Transition (EMT). We hypothesized that PMCs when stimulated with TGF-ß1 undergo EMT targeting E-cadherin and this transformation of PMC to myofibroblasts is dependent on miR-26a and smad-2 signaling. The expression of EMT markers such as fibroblast specific protein-1 (FSP-1) and collagen type I, E-cadherin, a-Smooth muscle actin (a-SMA), Vimentin, and Cytokeratin-8 were analyzed in PMC treated with TGF-ß1 or transfected with miR-26a. TGF-ß1 significantly up-regulated miR-26a expression in PMC, and transfection of miR-26a enhanced a-SMA and collagen type-1 expression while the E-cadherin expression was decreased. In addition, luciferase reporter assay was performed to confirm E-cadherin as a target of miR-26a in PMCs. Furthermore in PMC, silencing miR-26a using anti-sense 2'-O-methyl oligo attenuated a-SMA and enhanced E-cadherin in response to TGF-ß1. Consistent with the hypothesis, TGF-ß1 increased miR-26a expression in PMC, whereas knocking down of miR-26a attenuated smad-2 phosphorylation overtime in response to TGF-ß1. Taken together, these data indicate that miR-26a regulates the process of EMT in PMC which is mediated by TGF-ß1 and smad-2 signaling.

Original languageEnglish (US)
Pages (from-to)2927-2938
Number of pages12
JournalInternational Journal of Clinical and Experimental Pathology
Volume9
Issue number3
StatePublished - 2016
Externally publishedYes

Keywords

  • A-SMA
  • E-Cadherin
  • Epithelial-mesenchymal transition
  • Extra cellular matrix-proteins
  • MiR-26a
  • Pleural fibrosis
  • Pleural mesothelial cells
  • Smad-2
  • TGF-ß1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

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