NCBI Summary:
This gene is a member of the Ig superfamily and encodes a cell surface sialoglycoprotein expressed by cytokine-activated endothelium. This type I membrane protein mediates leukocyte-endothelial cell adhesion and signal transduction, and may play a role in the development of artherosclerosis and rheumatoid arthritis. Three alternatively spliced transcripts encoding different isoforms have been described for this gene. [provided by RefSeq, Dec 2010]
General function
Cell adhesion molecule
Comment
Cellular localization
Plasma membrane, Cytoskeleton
Comment
Adipokines and soluble cell adhesion molecules in insulin resistant and non-insulin resistant women with polycystic ovary syndrome. Koleva DI et al. (2016) Insulin resistance (IR) is closely associated with increased atherogenic risk. To investigate leptin, adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) levels and their relationship with each other and metabolic parameters in women with polycystic ovary syndrome (PCOS). The study included 76 PCOS women divided into insulin resistant and non-insulin resistant. Anthropometric parameters, glucose and lipid parameters, leptin, adiponectin, sICAM-1 and sVCAM-1 were determined. Homeostasis model of IR index(HOMA-IR), atherogenic index of plasma(AIP) and leptin/adiponectin ratio were calculated. HOMA-IR > 2.5 and/or fasting plasma glucose/immunoreactive insulin ratio < 0.333 were used as markers for IR. Non-insulin resistant PCOS had significantly higher adiponectin and sVCAM-1 levels. AIP was significantly higher in insulin resistant PCOS. Adiponectin showed a positive correlation with sVCAM-1 and sICAM-1. Insulin resistant PCOS women were at higher atherogenic risk compared to non-insulin resistant group. sVCAM-1 data confirms the necessity of further investigations for clarifying its role in IR.//////////////////
Ovarian function
Comment
Systemic inflammation, cellular influx and up-regulation of ovarian VCAM-1 expression in a mouse model of polycystic ovary syndrome (PCOS). Solano ME et al. PCOS, a major cause of anovulatory sterility, is associated with obesity, insulin resistance and chronic inflammation. New evidence suggests that the immune system aggravates the clinical features of PCOS. Our aim was to study the immune, metabolic and endocrine features of a mouse model of PCOS elicited by androgenisation using dehydroepiandrosterone (DHEA). We observed a significant weight gain and insulin resistance in DHEA-androgenised mice, coupled with the formation of ovarian follicular cysts. DHEA up-regulated the expression of vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 in the granulosa cell layer of the majority of cysts, and VCAM-1 expression in the theca cell layer of all follicles and cysts. The expression of these markers was low in control tissue. Peritoneal cells from PCOS-mice showed enhanced production of inflammatory cytokines, suggesting an association between chronic inflammation and PCOS. In addition, DHEA-androgenisation induced the activation of CD4(+) cells both in vivo and in vitro, and their expression of the respective ligands for VCAM-1 and ICAM-1, VLA-4 and LFA-1, as assessed in vitro. CD4(+) cells were present in androgenised ovaries, especially in the granulosa cell layer of cysts with high VCAM-1 expression. Herein, we present novel evidence that the immune system is activated systemically and locally in a mouse model for PCOS. We propose that VCAM-1 is involved in aggravating PCOS symptoms by promoting leukocyte recruitment to the ovaries and perpetuating local inflammation. These findings offer novel therapeutic opportunities for PCOS, such as blockage of VCAM-1 expression.
Expression regulated by
Steroids, Growth Factors/ cytokines
Comment
TGF-β1 inhibits microvascular-like formation by decreasing VCAM1 and ICAM1 via the upregulation of SNAIL in human granulosa cells. Li H et al. (2021) Three major endothelial cell junctional adhesion molecules (VCAM1, ICAM1 and E-SELECTIN) play important roles in the process of angiogenesis, a progression of extensive physiological vascularization that occurs during the formation of the corpus luteum. Our previous studies demonstrated that TGF-β1 is a negative regulator of luteinization and progesterone production in luteinized human granulosa (hGL) cells. Whether TGF-β1 can regulate the expression of these endothelial cell adhesion molecules and subsequent angiogenesis in hGL cells remains to be elucidated. Using dual inhibition approaches (small molecular inhibitors and siRNA-based knockdown), we provided the first data showing that TGF-β1 significantly upregulates the expression of the SNAIL transcription factor, which in turn suppresses the expression of VCAM1 and ICAM1 in hGL cells. Additionally, we demonstrate that the suppressive effects on the expression of VCAM1 and ICAM1 induced by TGF-β1 treatment were most likely via an ALK5-mediated SMAD-dependent signaling pathway. Furthermore, functional studies showed that hGL cells cultured on Matrigel exhibited two typical endothelial cell phenotypes, microvascular-like formation and a sprouting microvascular pattern. Notably, these phenotypes were significantly suppressed by either TGF-β1 treatment or knockdown of VCAM1 and ICAM1. Our findings suggest that TGF-β1 plays a potential role in the inhibition of granulosa cell angiogenesis by downregulating the expression of VCAM1 and ICAM1 during follicular development and corpus luteum formation.////////////////// VCAM1 is Induced in Ovarian Theca and Stromal Cells in a Mouse Model of Androgen Excess. Candelaria NR et al. (2019) Ovarian theca androgen production is regulated by the pituitary luteinizing hormone (LH) and intra-follicular factors. Enhanced androgen biosynthesis by theca cells contributes to polycystic ovary syndrome (PCOS) in women, but the ovarian consequences of elevated androgens are not completely understood. Our study documents the molecular events that are altered in the theca and stromal cells of mice exposed to high androgen levels, using the non-aromatizable androgen DHT. Changes in ovarian morphology and function were observed not only in follicles, but also in the stromal compartment. Genome-wide microarray analyses revealed marked changes in the ovarian transcriptome of DHT-treated females within one week. Particularly striking was the increased expression of vascular cell adhesion molecule 1 (Vcam1) specifically in the NR2F2/COUPTF-II lineage theca cells, not granulosa cells, of growing follicles and throughout the stroma of the androgen treated mice. This response was mediated by androgen receptors (AR) present in theca and stromal cells. Human theca-derived cultures expressed both AR and NR2F2 that were nuclear. VCAM1 mRNA and protein were higher in PCOS-derived theca cells compared to control theca and reduced markedly by the AR antagonist flutamide. In the DHT-treated mice, VCAM1 was transiently induced by equine gonadotropin (eCG), when androgen and estrogen biosynthesis peak in preovulatory follicles, and was potently suppressed by a superovulatory dose of human chorionic gonadotropin (hCG). High levels of VCAM1 in the theca and interstitial cells of DHT-treated mice and in adult Leydig cells indicate that there may be novel functions for VCAM1 in reproductive tissues, including the gonads.//////////////////
Polycystic ovary syndrome (PCOS) affects 5% of reproductive aged women and is the leading cause of anovulatory infertility. A hallmark of PCOS is excessive theca cell androgen secretion, which is directly linked to the symptoms of PCOS. Our previous studies demonstrated that theca cells from PCOS ovaries maintained in long term culture persistently secrete significantly greater amounts of androgens than normal theca cells, suggesting an intrinsic abnormality. Furthermore, previous studies suggested that ovarian hyperandrogenemia is inherited as an autosomal dominant trait. However, the genes responsible for ovarian hyperandrogenemia of PCOS have not been identified. In this present study, Wood JR, et al carried out microarray analysis to define the gene networks involved in excess androgen synthesis by the PCOS theca cells in order to identify candidate PCOS genes. Analysis revealed that PCOS theca cells have a gene expression profile that is distinct from normal theca cells. Included in the cohort of genes with increased mRNA abundance in PCOS theca cells were aldehyde dehydrogenase 6 and retinol dehydrogenase 2, which play a role in all-trans-retinoic acid biosynthesis and the transcription factor GATA6. We demonstrated that retinoic acid and GATA6 increased the expression of 17alpha-hydroxylase, providing a functional link between altered gene expression and intrinsic abnormalities in PCOS theca cells. Thus, the analyses have 1) defined a stable molecular phenotype of PCOS theca cells, 2) suggested new mechanisms for excess androgen synthesis by PCOS theca cells, and 3) identified new candidate genes that may be involved in the genetic etiology of PCOS. This is one of the genes with Altered mRNA Abundance in PCOS Theca Cells as compared with normal theca cells Maintained Under Basal Conditions.
Ovarian localization
Theca, PBMC
Comment
Expression Levels of Vascular Cell Adhesion Molecule-1 in Young and Nonobese Women with Polycystic Ovary Syndrome. Seow KM et al. Background/Aims: The objective of this study was to measure levels of mRNAs for inflammatory markers and resistin in human peripheral blood mononuclear cells (PBMCs) in young and nonobese women with polycystic ovary syndrome (PCOS). Methods: Fifteen young, nonobese women with PCOS and 10 age-matched controls were enrolled in this study. Levels of mRNAs for resistin and the inflammatory markers interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in human PBMCs were measured using real-time PCR. Results: The mean age and BMI of the women with PCOS were 27.54 6.3 years and 27.4 5.7, respectively. The women with PCOS had significantly higher fasting and 2-hour insulin levels, homeostasis model assessment of insulin resistance index (HOMA(IR)) and total cholesterol levels than the controls. VCAM-1 and ICAM-1 mRNA levels were significantly higher in women with PCOS than in controls, whereas no differences in resistin, IL-6, TNF-a and MCP-1 mRNA levels were observed between the groups. After adjusting for the BMI, only VCAM-1 mRNA levels were significantly higher in women with PCOS than in controls and correlated with the HOMA(IR) and total cholesterol. Conclusion: Elevated VCAM-1 in human PBMCs in young, nonobese women with PCOS is associated with insulin resistance, independent of the BMI.