期刊
ENDOCRINE METABOLIC & IMMUNE DISORDERS-DRUG TARGETS
卷 21, 期 8, 页码 1441-1452出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1871530320666200929142503
关键词
p53-fibrinolytic system; EMT; acute lung injury; lung fibrosis; Curcumin; Smad; non-smad proteins
资金
- Department of Biotechnology (DBT) Grant [BT/PR25198/MED/30/1896/2017]
- Yenepoya (Deemed to be University)
The study investigated the role of curcumin in lung injury and fibrosis, revealing its anti-fibrotic effects through modulation of the p53-fibrinolytic system in TGF01-mediated alveolar EMT.
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-01 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 TGF01 mediated p53-Fibrinolytic system regulating alveolar EMT leading to IPF. In the present study, the potential molecular mechanism of curcumin in TGF-01 mediated p53-fibrinolytic system in basal alveolar epithelial cells was explored. Objectives: To understand the potential molecular mechanism of curcumin in TGF-01 mediated p53-fibrinolytic system in basal alveolar epithelial cells. Methods: Basal alveolar epithelial cells were treated with TGF01 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 cur cumin on EMT markers, IL-17A, p53-smad interaction to investigate the anti-fibrotic role of curcumin. Results: The results indicated that TGF-01-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-01 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 TGF01 mediated p53-fibrinolytic system during alveolar injury in vitro.
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