Role of the Notch Signaling Pathway in Fibrosis of Denervated Skeletal Muscle
作者机构：Department of Orthopaedics Central HospitalHuang gang 438000 China Department of Orthopaedics Suizhou Hospital Hubei University of Medicine Suizhou 430072China The 457# Hospital ofPLA Wuhan 430000China Department of Hand Surgery Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China
出 版 物：《Current Medical Science》 (当代医学科学（英文）)
年 卷 期：2019年第39卷第3期
页 面：419-425页
核心收录：
学科分类：10[医学]
主 题：Notch signaling pathway sciatic nerve skeletal muscle fibrosis N-[N-(3,5- difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester Notch 1 Jagged 1 Hes 1 collagen I denervated muscular atrophy
摘 要：In order to investigate the role of the Notch signaling pathway in skeletal muscle fibrosis after nerve injury, 60 Sprague-Dawley rats were selected and divided randomly into a control and two experimental groups. Group A served as controls without any treatment. Rats in groups B were injected intraperitoneally with 0.2 mL PBS and those in group C were injected intraperitoneally with 0.2 mL PBS+100 ymol/L, 0.2 mL N-[N-(3,5-difluorophenacetyl)-l-alanyl]- S-phenylglycine t-butyl ester (DAPT, a gamma-secretase inhibitor that suppresses Notch signaling) respectively, on postoperative days 1, 3, 7, 10, and 14 in a model of denervation-induced skeletal muscle fibrosis by right sciatic nerve transection. Five rats from each group were euthanized on postoperative days 1, 7, 14, and 28 to collect the right gastrocnemii, and hematoxylin and eosin (HE) staining, immunohistochemistry test, real-time PCR, and Western blotting were performed to assess connective tissue hyperplasia and fibroblast density as well as expression of Notch 1, Jagged 1, and Notch downstream molecules Hes 1 and collagen I (COL I) on day 28. There was no significant difference in HE-stained fibroblast density between group B and C on postoperative day 1. However, fibroblast density was significantly higher in group B than in group C on postoperative days 7, 14, and 28. Notch 1, Jagged 1, Hes 1, and COL I proteins in the gastrocnemius were expressed at very low levels in group A but at high levels in group B. Expression levels of these proteins were significantly lower in group C than in group B (P0.05), but they were higher in group C than in group A (P0.05) on postoperative day 28. We are led to conclude that locking the Notch signaling pathway inhibits fibrosis progression of denervated skeletal muscle. Thus, it may be a new approach for treatment of fibrosis of denervated skeletal muscle.
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