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颗粒蛋白前体促进Sprague-Dawley大鼠硅胶所致包膜的形成与发展。

Progranulin Promotes the Formation and Development of Capsules Caused by Silicone in Sprague-Dawley Rats.

作者信息

Zhou Yongting, Pang Hao, Wang Jie, Wu Hao, Xu Zidi, Liu Xueyi, Xiao Zhibo

机构信息

Department of Plastic Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.

出版信息

Clin Cosmet Investig Dermatol. 2022 Aug 6;15:1561-1573. doi: 10.2147/CCID.S374128. eCollection 2022.

Abstract

BACKGROUND

Silicone implants are currently the most widely used artificial materials in plastic surgery. Capsule formation following implant application is unavoidable. When the capsule is excessively thick and strongly contracted, it can lead to obvious symptoms, clinically known as capsular contracture. Biological factors have always been the focus of research on the capsule formation. As a growth factor, progranulin (PGRN) plays an important regulatory role in wound healing, tissue fibrosis, tumor proliferation and invasion, and inflammation regulation. At present, the research on the capsule mainly involves the regulation of tissue healing and fibrosis under the influence of inflammation. Because PGRN has a regulatory role in these processes, we believe that the study of both can provide a new theoretical basis and intervention sites for monitoring and inhibiting the development of the capsule.

METHODS

In this experiment, the effects of different surgical operations on the content of PGRN in the surgical site and plasma of rats were detected. Sprague-Dawley (SD) rat dermal fibroblasts were co-cultured by recombinant PGRN. The effects of r-PGRN on fibroblasts were detected by 5-ethynyl-2'-deoxyuridine (EdU) assay, wound healing assay and Western blot assay. Finally, the effect of PGRN on capsule formation and contracture was studied by changing the content of PGRN in the prosthesis in rats after operation.

RESULTS

Surgical trauma and silicone implant increased plasma and local PGRN levels in SD rats. PGRN can activate the TGF-β/SMAD signaling pathway in a dose-dependent manner, thereby promoting fibroblast proliferation, differentiation and migration and inhibiting apoptosis and enhancing cell function, thereby promoting capsule formation and contracture.

CONCLUSION

PGRN promotes the formation and contracture of the silicone implant capsule in SD rats by activating the TGF-β/SMAD signaling pathway. This discovery may provide new therapeutic targets and detection indicators.

摘要

背景

硅胶植入物是目前整形外科中应用最广泛的人工材料。植入后形成包膜是不可避免的。当包膜过厚且强烈收缩时,可导致明显症状,临床上称为包膜挛缩。生物学因素一直是包膜形成研究的重点。颗粒蛋白前体(PGRN)作为一种生长因子,在伤口愈合、组织纤维化、肿瘤增殖与侵袭以及炎症调节中发挥着重要的调节作用。目前,关于包膜的研究主要涉及炎症影响下组织愈合和纤维化的调节。由于PGRN在这些过程中具有调节作用,我们认为对两者的研究可为监测和抑制包膜发展提供新的理论基础和干预位点。

方法

本实验检测了不同手术操作对大鼠手术部位和血浆中PGRN含量的影响。用重组PGRN共培养Sprague-Dawley(SD)大鼠皮肤成纤维细胞。通过5-乙炔基-2'-脱氧尿苷(EdU)检测法、伤口愈合检测法和蛋白质免疫印迹法检测r-PGRN对成纤维细胞的影响。最后,通过改变大鼠术后假体中PGRN的含量,研究PGRN对包膜形成和挛缩的影响。

结果

手术创伤和硅胶植入增加了SD大鼠血浆和局部PGRN水平。PGRN能以剂量依赖的方式激活TGF-β/SMAD信号通路,从而促进成纤维细胞增殖、分化和迁移,抑制细胞凋亡并增强细胞功能,进而促进包膜形成和挛缩。

结论

PGRN通过激活TGF-β/SMAD信号通路促进SD大鼠硅胶植入物包膜的形成和挛缩。这一发现可能提供新的治疗靶点和检测指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05ec/9365064/6cb435ec2ee2/CCID-15-1561-g0001.jpg

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