Modified insulin-like growth factor 1 containing collagen-binding domain for nerve regeneration

• Published in: Neural regeneration research Vol. 13; no. 2; pp. 298 - 303
• Main Authors: Li, Jian-an, Zhao, Chang-fu, Li, Shao-jun, Zhang, Jun, Li, Zhen-hua, Zhang, Qiao, Yang, Xiao-yu, Zan, Chun-fang
• Format: Journal Article
• Language: English
• Published: India Wolters Kluwer India Pvt. Ltd 01.02.2018; Medknow Publications and Media Pvt. Ltd; Medknow Publications & Media Pvt. Ltd; Department of Orthopedics, Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, Jilin Province, China%Department of Orthopedics, China-Japan Union Hospital, Jilin University, Changchun, Jilin Province, China%Department of Orthopedics, Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, Jilin Province, China%Department of Orthopedics, Second Hospital of Jilin University, Changchun, Jilin Province, China; Department of Orthopedics, Second Hospital of Jilin University, Changchun, Jilin Province, China; Medknow Publications & Media Pvt Ltd; Wolters Kluwer Medknow Publications
• Subjects: Cell growth; Chemical properties; Chromatography; Collagen; Deoxyribonucleic acid; DNA; Health aspects; Insulin-like growth factor I; Insulin-like growth factors; Nerve regeneration; nerve regeneration; insulin-like growth factor 1; collagen-binding domain; fusion protein; collagenase; targeted therapy; neural regeneration; Penicillin; Pharmaceutical chemistry; Pharmacological research; Plasmids; Proteins; Recombinant proteins; 神经生长;生长因素;骨胶原;胰岛素;绑定;新生;IGF-1;修改; United States > US; China; Germany; collagenase; targeted therapy; fusion protein; neural regeneration; collagen-binding domain; nerve regeneration; insulin-like growth factor 1
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/1673-5374.226400

Insulin-like growth factor 1 （IGF-I） is a potential nutrient for nerve repair. However, it is impractical as a therapy because of its limited half- life, rapid clearance, and limited target specificity. To achieve targeted and long-lasting treatment, we investigated the addition of a binding structure by fusing a collagen-binding domain to IGF- 1. After confirming its affinity for collagen, the biological activity of this construct was examined by measuring cell proliferation after transfection into PC12 and Schwann cells using a 3-（4,5-dimethyl-2-thiazolyl）-2,5-di- phenyl-2-H-tetrazolium bromide assay. Immunofluorescence staining was conducted to detect neurofilament and microtubule-associated protein 2 expression, while real time-polymerase chain reaction was utilized to determine IGF-1 receptor and nerve growth/actor mRNA expression. Our results demonstrate a significant increase in collagen-binding activity of the recombinant protein compared with IGF-1. Moreover, the recombinant protein promoted proliferation of PC12 and Schwann cells, and increased the expression of neurofilament and microtubule-associated protein 2. Importantly, the recombinant protein also stimulated sustained expression of IGF-1 receptor and nerve growth factor mRNA for days. These results show that the recombinant protein achieved the goal of targeting and long-lasting treatment, and thus could become a clinically used factor for promoting nerve regeneration with a prolonged therapeutic effect.