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Endocrine, Metabolic & Immune Disorders - Drug Targets


ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Research Article

Curcumin Targets p53-Fibrinolytic System in TGF-β1 Mediated Alveolar Epithelial Mesenchymal Transition in Alveolar Epithelial Cells

Author(s): Sadiya Bi Shaikh, Ashwini Prabhu and Yashodhar P. Bhandary*

Volume 21, Issue 8, 2021

Published on: 29 September, 2020

Page: [1441 - 1452] Pages: 12

DOI: 10.2174/1871530320666200929142503

Price: $65


Aims: We aim to investigate curcumin interaction with p53-fibrinolytic system, smad dependent and independent pathways underlying their prime role during lung injury and fibrosis.

Background: Curcumin, an active component of Curcuma longa plant, substantially modulates respiratory conditions. TGF-β1 plays a central role in lung remodeling by balancing extracellular matrix (ECM) production and degradation, which is a hallmark for alveolar EMT. However, the crosstalk of curcumin is not known yet with TGF- β1 mediated p53-Fibrinolytic system regulating alveolar EMT leading to IPF. In the present study, the potential molecular mechanism of curcumin in TGF-β1 mediated p53-fibrinolytic system in basal alveolar epithelial cells was explored.

Objectives: To understand the potential molecular mechanism of curcumin in TGF-β1 mediated p53-fibrinolytic system in basal alveolar epithelial cells.

Methods: Basal alveolar epithelial cells were treated with TGF- β1 to induce alveolar EMT and after 24 hrs curcumin was administered to study its anti-fibrotic effects. Molecular techniques like immunoblot, RT-PCR and immunofluorescence were performed to assess the anti-fibrotic role of curcumin on EMT markers, IL-17A, p53-smad interaction to investigate the anti-fibrotic role of curcumin.

Results: The results indicated that TGF-β1-induced EMT in A549 cells exhibited altered expression of the IL-17A, p53-fibrinolytic markers and EMT markers at the mRNA and protein level. Intervention with curcumin attenuated alveolar EMT and inactivated TGF-β1 induced Smad/non Smad signaling pathways via blocking p53-fibrinolytic system.

Conclusion: This study provides the first evidence of the dynamic response of curcumin on TGF- β1 mediated p53-fibrinolytic system during alveolar injury in vitro.

Keywords: p53-fibrinolytic system, EMT, acute lung injury, lung fibrosis, Curcumin, Smad/non-smad proteins.

Graphical Abstract

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