The role of halofuginone in fibrosis: more to be explored?

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

Luo, Di¹  Xie, Xiaoyan²  Gao, Yijun²  Wang, Yuan³ 

[1] and;Department of Stomatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China;Xiangya School of Stomatology, Central South University, Changsha, Hunan Province, China

关键词: myofibroblast;    Th17;    TGF‐;    β    extracellular matrix;    collagen;   

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Fibrosis, which can be defined as an abnormal or excessive accumulation of extracellular matrix (ECM), particularly fibrillar collagens, is a key driver of progressive organ dysfunction in many inflammatory and metabolic diseases, including idiopathic pulmonary fibrosis (IPF), cirrhosis, nephropathy, and oral submucous fibrosis (OSF). It has been estimated to contribute to ∼45% of deaths in the developed world. Therefore, agents that target specific fibrotic pathways, with the consequence of slowing, arresting, or even reversing the progression of tissue fibrogenesis, are urgently needed. 7-Bromo-6-chloro-3-[3-(3-hydroxy-2-piperidinyl)-2-oxopropyl]-4(3H)-quinazolinone (halofuginone), an analog of febrifugine, which specifically targets the pathogenesis of ECM proteins, inhibits tissue fibrosis and regeneration and even affects the development of tumors in various tissues. Four modes of actions of halofuginone against fibrosis have been presented: 1) Inhibition of mothers against decapentaplegic homolog 3 (Smad3) phosphorylation downstream of the TGF-β signaling pathway, 2) reduction of collagen amounts, 3) decreases in ECM protein, and 4) selective prevention of Th17 cell differentiation. In this review, we will mainly focus on the rationale for halofuginone against fibrosis.

【 授权许可】

CC BY