IKVAV peptide-containing hydrogel decreases fibrous scar after spinal cord injury by inhibiting fibroblast migration and activation

Tao Jiang; Shitong Li; Benchang Xu; Kun Liu; Tong Qiu; Honglian Dai

doi:10.1016/j.bbr.2023.114683

IKVAV peptide-containing hydrogel decreases fibrous scar after spinal cord injury by inhibiting fibroblast migration and activation

Behav Brain Res. 2023 Oct 18:455:114683. doi: 10.1016/j.bbr.2023.114683. Epub 2023 Sep 24.

Authors

Tao Jiang¹, Shitong Li², Benchang Xu³, Kun Liu², Tong Qiu⁴, Honglian Dai⁵

Affiliations

¹ State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Biomedical Materials and Engineering Research Center of Hubei Province, Wuhan University of Technology, Wuhan 430070, China; School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan 430070, China.
² State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Biomedical Materials and Engineering Research Center of Hubei Province, Wuhan University of Technology, Wuhan 430070, China.
³ State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Biomedical Materials and Engineering Research Center of Hubei Province, Wuhan University of Technology, Wuhan 430070, China; School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan 430070, China; Institut WUT-AWU, Wuhan University of Technology, Wuhan 430070, China.
⁴ State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Biomedical Materials and Engineering Research Center of Hubei Province, Wuhan University of Technology, Wuhan 430070, China; School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan 430070, China; Institut WUT-AWU, Wuhan University of Technology, Wuhan 430070, China. Electronic address: tongttqq@whut.edu.cn.
⁵ State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Biomedical Materials and Engineering Research Center of Hubei Province, Wuhan University of Technology, Wuhan 430070, China; Foshan Xianhu Laboratory of the Advanced Energy Science and Technology Guangdong Laboratory, Xianhu Hydrogen Valley, Foshan 528200, China. Electronic address: daihonglian@whut.edu.cn.

PMID: 37751807
DOI: 10.1016/j.bbr.2023.114683

Abstract

Fibrous scar is one of the major factors that hinder functional recovery in patients with spinal cord injury (SCI). Studies have shown that the laminin α1 peptide chain ile-les-val-ala-Val (IKVAV) promoted axonal growth and motor function recovery in rats after SCI. However, whether IKVAV could ameliorate SCI via reducing the formation of fibrous scar was not clear. A SCI model was constructed by transecting the rat spinal cord with a scalpel and implanting poly (N-propan-2-ylprop-2-enamide) (PNIPAM)-b-poly (AC-PEG-COOH) (PNPP) or PNIPAM-b-poly (AC-PEG-IKVAV) (PNPP-IKVAV) hydrogel. 14 days later hematoxylin-eosin staining and immunohistochemical staining were used to assess the effect of PNPP-IKVAV on scar formation. The effect of PNPP-IKVAV on endoplasmic reticulum (ER) stress was investigated by immunohistochemical staining. NIH-3T3 cells were used for in vitro scratching experiments and a transforming growth factor 1 (TGF-β1) activation model was constructed to assess the role of PNPP-IKVAV. In this study, PNPP-IKVAV inhibited fibroblast migration and suppressed TGF-β1 activation and ER stress (ERS) to reduce the extracellular matrix secretion by fibroblasts.

Keywords: Endoplasmic reticulum stress; Fibrous scar; Nerve repair; Peptide; Spinal cord injury.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aniline Compounds
Animals
Cicatrix / drug therapy
Humans
Hydrogels* / pharmacology
Laminin
Mice
Organophosphorus Compounds
Peptide Fragments
Peptides / pharmacology
Rats
Spinal Cord
Spinal Cord Injuries* / complications
Spinal Cord Injuries* / drug therapy
Transforming Growth Factor beta1

Substances

Hydrogels
Transforming Growth Factor beta1
Peptides
isoleucyl-lysyl-valyl-alanyl-valine
Laminin
Peptide Fragments
4-aminophenylphosphate
Aniline Compounds
Organophosphorus Compounds