Desmuslin gene knockdown causes altered expression of phenotype markers and differentiation of saphenous vein smooth muscle cells.

Abstract

OBJECTIVE:

Phenotypic alterations of vascular smooth muscle cells (VSMCs) appear critical to the development of primary varicose veins. Previous study indicated desmuslin, an intermediate filament protein, was differentially expressed in smooth muscle cells (SMCs) isolated from varicose veins; thus, it was naturally hypothesized that altered desmuslin expression might in turn affect the functioning of VSMCs, leading to the phenotypic alterations and varicose vein development.

METHODS:

In this study, expression of desmuslin in normal human saphenous vein SMCs was knocked down using small interfering RNA (siRNA), and control cells were treated with a scrambled siRNA sequence. The levels of several phenotypic markers including smooth muscle (SM) alpha-actin and smooth muscle myosin heavy chain (SM-MHC) were assessed. Collagen formation, matrix metalloproteinase expression (MMP-2), and cytoskeletal and morphological changes were also examined.

RESULTS:

SMCs treated with desmuslin siRNA exhibited significantly increased levels of collagen synthesis and MMP-2 expression and decreased expression levels of SM alpha-actin, SM-MHC, and smoothelin and exhibited disassembly of actin stress fibers when compared with the control cells. Changes in cell morphology and actin fiber networks in VSMCs treated with desmuslin siRNA were consistent with a lower degree of differentiation.

CONCLUSIONS:

These results indicated desmuslin expression is required for the maintenance of VSMC phenotype. Decreased desmuslin expression may affect differentiation of VSMCs and ultimately contribute to the development of varicose veins.

• Authors: Ying Xiao, Zhibin Huang, Henghui Yin, Hui Zhang, Shenming Wang
• Journal: Journal of vascular surgery (J Vasc Surg) Vol. 52 Issue 3 Pg. 684-90 (Sep 2010) ISSN: 1097-6809 [Electronic] United States
• PMID: 20573469 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• Biomarkers
• Cytoskeletal Proteins
• Intermediate Filament Proteins
• Muscle Proteins
• SMTN protein, human
• desmuslin
• Collagen
• MMP2 protein, human
• Matrix Metalloproteinase 2
• Myosin Heavy Chains

Topics

• Actins (metabolism)
• Aged
• Biomarkers (metabolism)
• Cell Differentiation
• Cell Shape
• Cells, Cultured
• Collagen (biosynthesis)
• Cytoskeletal Proteins (metabolism)
• Down-Regulation
• Female
• Gene Knockdown Techniques
• Humans
• Intermediate Filament Proteins (genetics, metabolism)
• Male
• Matrix Metalloproteinase 2 (metabolism)
• Middle Aged
• Muscle Proteins (metabolism)
• Muscle, Smooth, Vascular (metabolism)
• Myocytes, Smooth Muscle (metabolism)
• Myosin Heavy Chains (metabolism)
• Phenotype
• RNA Interference
• Saphenous Vein (metabolism)
• Stress Fibers (metabolism)
• Transfection
• Varicose Veins (metabolism, pathology)