Behavioural Brain Research ( IF 2.6 ) Pub Date : 2023-09-24 , DOI: 10.1016/j.bbr.2023.114683 Tao Jiang 1 , Shitong Li 2 , Benchang Xu 3 , Kun Liu 2 , Tong Qiu 3 , Honglian Dai 4
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.
中文翻译:
含 IKVAV 肽的水凝胶通过抑制成纤维细胞迁移和活化来减少脊髓损伤后的纤维疤痕
纤维性疤痕是阻碍脊髓损伤(SCI)患者功能恢复的主要因素之一。研究表明,层粘连蛋白α1肽链ile-les-val-ala-Val(IKVAV)促进SCI后大鼠轴突生长和运动功能恢复。然而,IKVAV 是否可以通过减少纤维疤痕的形成来改善 SCI 尚不清楚。用手术刀横切大鼠脊髓,植入聚(N-丙-2-基丙-2-烯酰胺)(PNIPAM)-b-聚(AC-PEG-COOH)(PNPP)或PNIPAM-构建SCI模型。 b-聚(AC-PEG-IKVAV)(PNPP-IKVAV)水凝胶。14天后,使用苏木精-伊红染色和免疫组织化学染色来评估PNPP-IKVAV对疤痕形成的影响。通过免疫组织化学染色研究 PNPP-IKVAV 对内质网 (ER) 应激的影响。使用NIH-3T3细胞进行体外划痕实验,构建转化生长因子1(TGF-β1)激活模型来评估PNPP-IKVAV的作用。在这项研究中,PNPP-IKVAV 抑制成纤维细胞迁移并抑制 TGF-β1 激活和 ER 应激 (ERS),从而减少成纤维细胞的细胞外基质分泌。