Identification and Characterization of a Novel Nanobody Against Human CTGF to Reveal Its Antifibrotic Effect in an in vitro Model of Liver Fibrosis

被引：2

作者：

Liu, Rong ^{[1
]}

Zhu, Min ^{[2
]}

Chen, Jiaojiao ^{[3
]}

Gai, Junwei ^{[2
]}

Huang, Jing ^{[2
]}

Zhou, Yingqun ^{[1
]}

Wan, Yakun ^{[2
]}

Tu, Chuantao ^{[4
]}

机构：

[1] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Gastroenterol, Shanghai 200072, Peoples R China

[2] Shanghai Novamab Biopharmaceut Co Ltd, Shanghai 201318, Peoples R China

[3] Tongji Univ, Shanghai Peoples Hosp 4, Dept Gastroenterol, Sch Med, Shanghai 200434, Peoples R China

[4] Fudan Univ, Shanghai Publ Hlth Clin Ctr, Dept Gastroenterol, Shanghai 201508, Peoples R China

来源：

INTERNATIONAL JOURNAL OF NANOMEDICINE | 2023年 / 18卷

基金：

中国国家自然科学基金; 上海市自然科学基金;

关键词：

nanobody; connective tissue growth factor; liver fibrosis; hepatic stellate cells; TISSUE GROWTH-FACTOR; MONOCLONAL-ANTIBODY; EXPRESSION; MECHANISMS;

D O I：

10.2147/IJN.S428430

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

Background: No agents are currently available for the treatment or reversal of liver fibrosis. Novel antifibrotic therapies for chronic liver diseases are thus urgently needed. Connective tissue growth factor (CTGF) has been shown to contributes profoundly to liver fibrogenesis, which makes CTGF as a promising target for developing antifibrotic agents. Methods: In this study, we identified a novel nanobody (Nb) against human CTGF (anti-CTGF Nb) by phage display using an immunized camel, which showed high affinity and specificity in vitro. LX-2 cells, the immortalized human hepatic stellate cells, were induced by transforming growth factor beta1 (TGF & beta;1) as an in vitro model of liver fibrosis to verify the antifibrotic activity of the anti-CTGF Nb. Results: Our data demonstrated that anti-CTGF Nb effectively alleviated TGF & beta;1-induced LX-2 cell proliferation, activation, and migration, and promoted the apoptosis of activated LX-2 cells in response to TGF & beta;1. Moreover, the anti-CTGF Nb remarkably reduced the levels of TGF & beta;1, Smad2, and Smad3 expression in LX-2 stellate cells stimulated by TGF & beta;1. Conclusion: Taken together, we successfully identified a novel Nb against human CTGF, which exhibited antifibrotic effects in vitro by regulating the biological functions of human stellate cells LX-2.

引用

页码：5407 / 5422

页数：16

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