Expression of pro-fibrotic and anti-fibrotic molecules in dimethylnitrosamine-induced hepatic fibrosis

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• 作者：Roberta Sferra^a ; ¹ ; ^{roberta.sferra@univaq.it} ; Antonella Vetuschi^a ; ¹ ; ^{antonella.vetuschi@univaq.it} ; Simona Pompili^a ; ^{pompili.simona@virgilio.it} ; Eugenio Gaudio^b ; ^{eugenio.gaudio@uniroma1.it} ; Silvia Speca^c ; ^{silviaspeca@gmail.com} ; Giovanni Latella^c ; ^{giolatel@tin.it}
• 关键词：Liver fibrosis ; CTGF ; Integrins ; mTOR ; PPARγ ; TGF-β
• 刊名：Pathology - Research and Practice
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：213
• 期：1
• 页码：58-65
• 全文大小：3212 K
• 卷排序：213

文摘

Hepatic fibrosis is characterized by a progressive accumulation of fibrillar extracellular matrix (ECM) proteins, produced by activated myofibroblasts which are modulated by both profibrotic and antifibrotic factors.ObjectiveTo evaluate in vivo the expression of pro-fibrotic molecules like avβ6 integrin, transforming growth factor-β (TGF-β), Smad3, connective tissue growth factor (CTGF) and mammalian target of Rapamycin (mTOR), as well as anti-fibrotic peroxisome proliferator-activated receptor-γ (PPARγ) in an experimental model of chronic hepatitis-associated fibrosis induced by intraperitoneal administration of dimethylnitrosamine (DMN) in mice.MethodsChronic hepatitis was induced in 12 Smad3 wild-type (WT) and 12 knock-out (KO) mice by intraperitoneal DMN administration. Histological, morphometric and immunohistochemical analyses using α-smooth muscle actin (α-SMA), collagen types I–III, TGF-β1, Smad3, avβ6 integrin, CTGF, mTOR and PPARγ antibodies were performed.ResultsThe liver of DMN-treated Smad3 WT mice showed a higher degree of hepatic accumulation of connective tissue compared to KO mice. The expression of α-SMA, collagen I–III and CTGF was increased in Smad3 WT compared to KO mice treated with DMN, associated with a concomitant up-regulation of avβ6, TGFβ, Smad3, and mTOR and a reduction in PPARγ expression.ConclusionsThese results suggest a possible interaction between pro-fibrotic and anti-fibrotic molecules in the development of hepatic fibrosis.