PKG1 促进 HIV 诱导的痔疮血管平滑肌细胞的增殖、迁移和纤维化。

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

机构信息

Department of Pathology, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University, The First Hospital of Changsha, Changsha City, Hunan Province, China.

Department of Infectious and Immunology, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University, The First Hospital of Changsha, Changsha City, Hunan Province, China.

出版信息

Int J Colorectal Dis. 2024 Oct 31;39(1):175. doi: 10.1007/s00384-024-04743-3.

DOI:10.1007/s00384-024-04743-3

PMID:39477875

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11525407/

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.

摘要

背景

人类免疫缺陷病毒（HIV）感染患者中痔非常常见。HIV 阳性患者术后感染风险明显高于 HIV 阴性个体，且伤口愈合时间明显延长。本研究旨在从血管平滑肌细胞（VSMC）功能的角度探讨 HIV 相关性痔的作用。

方法

本研究共收集 24 例痔组织标本（注：无 IV 度痔），进行 Masson 染色评估纤维化。通过 qPCR 和 WB 分析分别监测 mRNA 和蛋白水平。免疫荧光评估 PKG1 和 α-SMA 表达。体外建立细胞模型，用 HIV 包膜糖蛋白（gp）120 刺激 VSMCs，gp120 是一种 HIV 包膜蛋白。通过 CCK-8 检测和 EdU 染色评估细胞增殖。此外，进行伤口愈合实验评估细胞迁移。

结果

我们的数据证实，HIV 感染患者痔组织存在纤维化，PKG1 表达上调。此外，HIV gp120 的给药促进了 VSMCs 的增殖和迁移。同样，纤维化相关标志物（α-SMA、MMP2、MMP3 和 TIMP1）也明显上调。然而，沉默 PKG1 抑制了 gp120 刺激的 VSMCs 中增殖、迁移和纤维化相关标志物的表达。