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骨形态发生蛋白-7通过激活骨形态发生蛋白-7/信号转导分子1/5/8信号通路来抑制过度的瘢痕形成。

BMP‑7 suppresses excessive scar formation by activating the BMP‑7/Smad1/5/8 signaling pathway.

作者信息

Guo Jingdong, Lin Quan, Shao Ying, Rong Li, Zhang Duo

机构信息

Department of Plastic and Reconstructive Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.

出版信息

Mol Med Rep. 2017 Aug;16(2):1957-1963. doi: 10.3892/mmr.2017.6779. Epub 2017 Jun 14.

DOI:10.3892/mmr.2017.6779
PMID:28627680
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5561965/
Abstract

Scarring is the inevitable consequence of wound repair, which may cause significant physical and mental pain to patients when excessive. Bone morphogenetic protein‑7 (BMP‑7) has been proved to inhibit TGF‑β‑induced fibrosis in various tissues including dermal papilla cells. However, the effect of BMP‑7 on hypertrophic scarring, a common proliferative disorder of dermal fibroblasts, has not been determined. To overcome this problem, the present study established a mouse model of thermal injury to investigate the inhibitory effects of BMP‑7 on scar formation. The histological analysis of scar tissues was performed by H&E and Masson's trichrome staining. Western blot assay was used to determine the level changes of related proteins and TUNEL assay was performed to assess the apoptosis of scar tissues. The results demonstrated that BMP‑7 promoted wound healing and inhibited scar formation when compared with untreated mice. Collagen deposition and the expression of fibrotic proteins were suppressed in the scar tissues of mice treated with BMP‑7. In addition, BMP‑7 induced fibroblast apoptosis in scar tissues. Furthermore, activation of the BMP‑7/Smad1/5/8 signaling pathway may have been involved in the inhibitory effects of BMP‑7 on scar formation. In conclusion, the results of the present study indicate that BMP‑7 may inhibit excessive scar formation via activation of the BMP‑7/Smad1/5/8 signaling pathway. The results present a potential alternative therapeutic strategy for the treatment of hypertrophic scarring.

摘要

瘢痕形成是伤口修复的必然结果,过度时可能给患者带来巨大的身心痛苦。骨形态发生蛋白-7(BMP-7)已被证明可抑制包括真皮乳头细胞在内的各种组织中转化生长因子-β(TGF-β)诱导的纤维化。然而,BMP-7对肥厚性瘢痕(一种常见的真皮成纤维细胞增殖性疾病)的影响尚未确定。为克服这一问题,本研究建立了热损伤小鼠模型,以研究BMP-7对瘢痕形成的抑制作用。通过苏木精-伊红(H&E)染色和马松三色染色对瘢痕组织进行组织学分析。采用蛋白质免疫印迹法检测相关蛋白水平变化,并用末端脱氧核苷酸转移酶介导的缺口末端标记法(TUNEL法)评估瘢痕组织的细胞凋亡情况。结果表明,与未处理的小鼠相比,BMP-7促进了伤口愈合并抑制了瘢痕形成。在接受BMP-7治疗的小鼠瘢痕组织中,胶原蛋白沉积和纤维化蛋白的表达受到抑制。此外,BMP-7诱导瘢痕组织中的成纤维细胞凋亡。此外,BMP-7/Smad1/5/8信号通路的激活可能参与了BMP-7对瘢痕形成的抑制作用。总之,本研究结果表明,BMP-7可能通过激活BMP-7/Smad1/5/8信号通路来抑制过度的瘢痕形成。这些结果为肥厚性瘢痕的治疗提供了一种潜在的替代治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7551/5561965/421ad8a0413e/MMR-16-02-1957-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7551/5561965/13c2bb8c1145/MMR-16-02-1957-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7551/5561965/78f58679d1a5/MMR-16-02-1957-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7551/5561965/6b33a9e14769/MMR-16-02-1957-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7551/5561965/3a013a35f09b/MMR-16-02-1957-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7551/5561965/421ad8a0413e/MMR-16-02-1957-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7551/5561965/13c2bb8c1145/MMR-16-02-1957-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7551/5561965/78f58679d1a5/MMR-16-02-1957-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7551/5561965/6b33a9e14769/MMR-16-02-1957-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7551/5561965/3a013a35f09b/MMR-16-02-1957-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7551/5561965/421ad8a0413e/MMR-16-02-1957-g04.jpg

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