PKG1 promotes the HIV-induced proliferation, migration, and fibrosis of vascular smooth muscle cells of hemorrhoids.

IF 2.5 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

International Journal of Colorectal Disease Pub Date : 2024-10-31 DOI:10.1007/s00384-024-04743-3

Zhen Li, Zhong Chen, Chun Liu, Shuang Peng, Ning Wang

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引用次数: 0

Abstract

Background: Hemorrhoids are very common in patients with human immunodeficiency virus (HIV) infection. The risk of postoperative infection is significantly greater in HIV-positive patients than in HIV-negative individuals, and the wound healing time is significantly prolonged. This study aimed to investigate the role of HIV-associated hemorrhoids from the perspective of vascular smooth muscle cell (VSMC) function.

Methods: A total of 24 hemorrhoid tissue samples (note: grade IV hemorrhoids were absence) were collected and subjected to Masson staining to evaluate fibrosis in this study. mRNA and protein levels were monitored by qPCR and WB analysis, respectively. Immunofluorescence was conducted to evaluate PKG1 and α-SMA expression. To establish a cell model in vitro, VSMCs were stimulated with envelope glycoprotein (gp) 120, which is a type of HIV envelope protein. Cell proliferation was assessed via a CCK-8 assay and EdU staining. Moreover, a wound healing assay was performed to assess cell migration.

Results: Our data confirmed that fibrosis was present in hemorrhoid tissues from HIV-infected patients and that PKG1 expression was upregulated. Moreover, the administration of HIV gp120 promoted the proliferation and migration of VSMCs. Similarly, fibrosis-related markers (α-SMA, MMP2, MMP3, and TIMP1) were markedly upregulated. However, silencing PKG1 inhibited the proliferation, migration, and expression of fibrosis-related markers in gp120-challenged VSMCs.

Conclusion: The present research revealed that PKG1 regulated the proliferation, migration, and fibrosis of VSMCs, thereby exerting detrimental effects on HIV-associated hemorrhoids.

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PKG1 促进艾滋病毒诱导的痔疮血管平滑肌细胞增殖、迁移和纤维化。

背景：痔疮在人类免疫缺陷病毒（HIV）感染患者中非常常见。HIV 阳性患者术后感染的风险明显高于 HIV 阴性患者，伤口愈合时间也明显延长。本研究旨在从血管平滑肌细胞（VSMC）功能的角度研究艾滋病毒相关性痔疮的作用：本研究共收集了 24 份痔疮组织样本（注：不包括 IV 级痔疮），并采用 Masson 染色法评估纤维化情况。免疫荧光法评估 PKG1 和 α-SMA 的表达。为了在体外建立细胞模型，用包膜糖蛋白（gp）120（一种 HIV 包膜蛋白）刺激 VSMC。细胞增殖通过 CCK-8 试验和 EdU 染色进行评估。此外，还进行了伤口愈合试验以评估细胞迁移：结果：我们的数据证实，HIV 感染者的痔疮组织存在纤维化，PKG1 表达上调。此外，HIV gp120 能促进 VSMC 的增殖和迁移。同样，纤维化相关标记物（α-SMA、MMP2、MMP3 和 TIMP1）也明显上调。然而，沉默PKG1可抑制gp120挑战的VSMCs的增殖、迁移和纤维化相关标志物的表达：本研究揭示了PKG1调控VSMCs的增殖、迁移和纤维化，从而对HIV相关性痔疮产生不利影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Colorectal Disease 医学-外科

CiteScore

4.90

自引率

3.60%

发文量

206

审稿时长

3-8 weeks

期刊介绍： The International Journal of Colorectal Disease, Clinical and Molecular Gastroenterology and Surgery aims to publish novel and state-of-the-art papers which deal with the physiology and pathophysiology of diseases involving the entire gastrointestinal tract. In addition to original research articles, the following categories will be included: reviews (usually commissioned but may also be submitted), case reports, letters to the editor, and protocols on clinical studies. The journal offers its readers an interdisciplinary forum for clinical science and molecular research related to gastrointestinal disease.