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Anti-fibrotic Effects of Tannic Acid Through Regulation of a Sustained TGF-beta Receptor Signaling

Anti-fibrotic Effects of Tannic Acid Through Regulation of a Sustained TGF-beta Receptor Signaling

Eleanor B Reed, Shawn Ard, Jennifer La, Chan Young Park, Laura Culligan, Jeffrey J Fredberg, Larisa V Smolyaninova, Sergei N Orlov, Bohao Chen, Robert Guzy, Gökhan M Mutlu, Nickolai O Dulin

Respir Res. 2019 Jul 29;20(1):168.

PMID: 31358001

Abstract:

Background:
Pulmonary fibrosis is a progressive disease characterized by structural distortion of the lungs. Transforming growth factor-beta (TGF-beta) is a key cytokine implicated in the pathogenesis of pulmonary fibrosis. TGF-beta-induced myofibroblast differentiation characterized by expression of smooth muscle alpha-actin and extracellular matrix proteins is a key process in pathogenesis of fibrotic disease. Tannic acid is a natural polyphenol with diverse applications. In this study, we investigated the effect of tannic acid on myofibroblast differentiation and pulmonary fibrosis in cultured cells and in bleomycin model of the disease.
Methods:
Primary cultured human lung fibroblasts (HLF) were used. The relative levels of proteins were determined by Western blotting. HLF contraction was measured by traction microscopy. Bleomycin-induced pulmonary fibrosis in mice was used as the disease model.
Results:
Tannic acid inhibited TGF-beta-induced expression of collagen-1 and smooth muscle alpha-actin (SMA) as well as force generation by HLF. Tannic acid did not affect initial phosphorylation of Smad2 in response to TGF-beta, but significantly inhibited sustained Smad2 phosphorylation, which we recently described to be critical for TGF-beta-induced myofibroblast differentiation. Accordingly, tannic acid inhibited Smad-dependent gene transcription in response to TGF-beta, as assessed using luciferase reporter for the activity of Smad-binding elements. Finally, in mouse model of bleomycin-induced pulmonary fibrosis, therapeutic application of tannic acid resulted in a significant reduction of lung fibrosis, decrease in collagen-1 content and of Smad2 phosphorylation in the lungs.
Conclusions:
This study demonstrates the anti-fibrotic effect of tannic acid in vitro and in vivo through a regulation of sustained Smad2 phosphorylation.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1401554	Tannic acid		1401-55-4	Price

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