Reciprocal Regulation of TGF-β and Reactive Oxygen Species: A Perverse Cycle for Fibrosis

Overview

Journal Redox Biol

Specialties Biology
Cell Biology
Endocrinology

Date 2015 Oct 27

PMID 26496488

Citations 292

Authors

Rui-ming Liu

Leena P Desai

Affiliations

Soon will be listed here.

Abstract

Transforming growth factor beta (TGF-β) is the most potent pro-fibrogenic cytokine and its expression is increased in almost all of fibrotic diseases. Although signaling through Smad pathway is believed to play a central role in TGF-β's fibrogenesis, emerging evidence indicates that reactive oxygen species (ROS) modulate TGF-β's signaling through different pathways including Smad pathway. TGF-β1 increases ROS production and suppresses antioxidant enzymes, leading to a redox imbalance. ROS, in turn, induce/activate TGF-β1 and mediate many of TGF-β's fibrogenic effects, forming a vicious cycle (see graphic flow chart on the right). Here, we review the current knowledge on the feed-forward mechanisms between TGF-β1 and ROS in the development of fibrosis. Therapeutics targeting TGF-β-induced and ROS-dependent cellular signaling represents a novel approach in the treatment of fibrotic disorders.

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