Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The Role of Erythrocyte Membrane Protein Band 4.1-Like 3 in Idiopathic Pulmonary Fibrosis

Version 1 : Received: 10 May 2023 / Approved: 11 May 2023 / Online: 11 May 2023 (03:44:24 CEST)

A peer-reviewed article of this Preprint also exists.

Kim, M.K.; Lee, J.-U.; Lee, S.J.; Chang, H.S.; Park, J.-S.; Park, C.-S. The Role of Erythrocyte Membrane Protein Band 4.1-like 3 in Idiopathic Pulmonary Fibrosis. Int. J. Mol. Sci. 2023, 24, 10182. Kim, M.K.; Lee, J.-U.; Lee, S.J.; Chang, H.S.; Park, J.-S.; Park, C.-S. The Role of Erythrocyte Membrane Protein Band 4.1-like 3 in Idiopathic Pulmonary Fibrosis. Int. J. Mol. Sci. 2023, 24, 10182.

Abstract

Novel genetic and epigenetic factors involved in the development and prognosis of idiopathic pulmonary fibrosis (IPF) have been identified. We previously observed that EPB41L3 increased in the lung fibroblasts of IPF patients. Thus, we investigated the role of EPB41L3 in IPF by comparing EPB41L3 mRNA and protein expression of lung fibroblast between patients with IPF and controls. We also investigated the regulation of the epithelial-mesenchymal transition (EMT) in an epithelial cell line (A549), and the fibroblast-to-myofibroblast transition (FMT) in a fibroblast cell line (MRC5), by overexpressing and silencing EPB41L3. EPB41L3 mRNA and protein levels, as measured by RT-PCR, real-time PCR, and western blot, were significantly higher in fibroblasts derived from 14 IPF patients than in those from 10 controls. The mRNA and protein expression of EPB41L3 was upregulated during transforming growth factor-β-induced EMT and FMT. Overexpression of EPB41L3 in A549 cells using lenti-EPB41L3 transfection suppressed the mRNA and protein expression of N-cadherin and COL1A1. Treatment with EPB41L3 siRNA upregulated mRNA and protein expression of N-cadherin. Overexpression of EPB41L3 in MRC5 cells using lenti-EPB41L3 transfection suppressed mRNA and protein expression of fibronectin and α-SMA. Finally, treatment with EPB41L3 siRNA upregulated mRNA and protein expression of FN1, COL1A1, and VIM. Overall, these data strongly support an inhibitory effect of EPB41L3 on the process of fibrosis and suggest therapeutic potential of EPB41L3 as an anti-fibrotic mediator.

Keywords

EPB41L3; Lung; Fibrosis; Epithelium; Mesenchyme; Fibroblast; Myofibroblast; Transition

Subject

Medicine and Pharmacology, Pulmonary and Respiratory Medicine

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