Regulated expression of matrix metalloproteinases, inflammatory mediators, and endometrial matrix remodeling by 17beta-estradiol in the immature rat uterus

Russo, L. A.; Peano, Bryan J.; Trivedi, Shreya P; Cavalcanto, Todd D.; Olenchock, Benjamin A.; Caruso, Joseph A.; Smolock, Amanda R.; Vishnevsky, Oleg; Gardner, Russell

doi:10.1186/1477-7827-7-124

Cited by 37 publications

(28 citation statements)

References 59 publications

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“…In agreement with previous studies, we found that estrogen supplementation prevented the downregulation of MMP-2 in the acute and chronic stages of LV remodeling (8,61). Similar estrogenic effects on MMP-2 expression were found in the ventricle and arteries of ovariectomized rats (27,61,64), rat uterus (48), and in cell culture studies (9,18). Estrogen also has a direct regulatory effect on MMP-2 expression in cardiac fibroblasts and vascular smooth muscle cells (18,34,53).…”

Section: Discussionsupporting

confidence: 79%

Estrogen improves TIMP-MMP balance and collagen distribution in volume-overloaded hearts of ovariectomized females

Voloshenyuk

Gardner

2010

American Journal of Physiology-Regulatory, Integrative and Comp

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Our previous studies demonstrate that 17␤-estradiol limits chronic volume overload-induced hypertrophy and improves heart function in ovariectomized rats. One possible cardioprotective mechanism involves the interaction between estrogen, estrogen receptors, and proteins of the extracellular matrix (ECM). The impact of estrogen deficiency and replacement on left ventricular (LV) hypertrophy and ECM protein expression was studied using five female rat groups: intact sham-operated, ovariectomized sham-operated, intact with volume overload, ovariectomized with volume overload, and ovariectomized with volume overload treated with estrogen. After 8 wk, LV protein extracts were evaluated by Western blot analysis for matrix metalloproteinase-2 (MMP-2) and MMP-9, MT1-MMP, tissue inhibitors of MMPs (TIMP)-1, TIMP-2, TIMP-3 and TIMP-4, collagens type I and III, and estrogen receptor ␣ and ␤ expression. MMP proteolytic activity was assessed by zymography. All volume-overloaded groups exhibited LV hypertrophy, which was associated with a loss of interstitial collagen and perivascular fibrosis. After 8 wk of volume overload, 70% of ovariectomized rats developed heart failure, in contrast to only one intact rat. A downregulation of MMP-2, estrogen receptor-␣ (ER␣), and ER␤, and upregulation of MMP-9 and MT1-MMP were found in the volume-overloaded hearts of ovariectomized rats. Estrogen treatment improved TIMP-2/MMP-2 and TIMP-1/MMP-9 protein balance, restored ER␣ expression, and prevented MMP-9 activation, perivascular collagen accumulation and development of heart failure. However, estrogen did not fully restore ER␤ expression and did not prevent the increase of MMP-9 expression or loss of interstitial collagen. These results support that estrogen limits undesirable ECM remodeling and LV dilation, in part, through modulation of ECM protein expression in volume-overloaded hearts of ovariectomized rats. extracellular matrix remodeling; ovariectomy; gender; hypertrophy; hormone; collagen; MT1-MMP; ventricle THE RISKS AND BENEFITS ASSOCIATED with estrogen replacement therapy remain uncertain. Conflicting results regarding the effect of estrogen replacement on the outcome of cardiovascular disease have been obtained from population studies, animal models, and clinical trials (2,16,20,21,32,33,61). The inconsistency of these findings demonstrates the lack of understanding of the mechanisms by which estrogen exerts its beneficial effects on the cardiovascular system. Using a rodent model, we demonstrated that hearts of intact female rats are resistant to chronic volume overload-induced adverse cardiac remodeling and dysfunction (12). This apparent cardioprotection is lost following ovariectomy (6). Estrogen replacement delays the development of left ventricular (LV) hypertrophy and dilation, and it prevents the onset of congestive heart failure (CHF) in ovariectomized rats with volume overload (13). However, the mechanisms of estrogen's protective effects in prevention of adverse myocardial remodeling remain unclear.Changes in extra...

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Section: Discussionsupporting

confidence: 79%

Estrogen improves TIMP-MMP balance and collagen distribution in volume-overloaded hearts of ovariectomized females

Voloshenyuk

Gardner

2010

American Journal of Physiology-Regulatory, Integrative and Comp

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“…KEGG analysis demonstrated that MMP9, CDC42 and IL8 were enriched in more than one pathway, which indicates that these genes serve as the pitch points of these pathways and are crucial for the formation of sexual differences in GBS. MMP9 directly induces the destruction of the extracellular matrix, participates in processes related to leukocyte migration, tumour cells migration, pathogenic E. coli infection, and is related to the deterioration of patients with GBS [5,[7][8][9]. CDC42 can mediate its effects through protein kinase A (PKA), regulate the intracellular activity of focal adhesions and up-regulate the expression of MMP9; as a result, this gene is considered a key factor regulating the interaction between cells and the extracellular matrix [23].…”

Section: Genome-wide Expression Differences Between Male and Female Gmentioning

confidence: 99%

“…Matrix metalloproteinases (MMPs) and tumour necrosis factor (TNF) are highly involved in the demyelinating process of GBS and are associated with disease severity and electrophysiological changes in GBS patients [5,[7][8][9]. MMP9 is highly associated with the transmigration process of inflammatory cells and the degradation of the blood-nerve barrier, while TNF-alpha is related to a cascade of events leading to immune-mediated demyelination and axonal damage, which constitute the two main pathophysiologic processes of GBS [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Genome-wide gene expression analysis of peripheral leukocytes in relation to the male predominance of Guillain–Barre syndrome: differential gene expression between male and female patients

Yin

Sun

Chen

et al. 2015

International Journal of Neuroscience

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“…It may be worthwhile to mention that estrogen is linked with neoplastic processes of different sites such as the breast, ovary, and endometrium [11][12][13]. Never theless, a growing body of evidence suggests a close association between estrogen and various MMPs, which cleave and remodel the ECM and thereby play a crucial role in tumor progression [14][15][16]. In breast cancer, estrogen was found to modulate tumor MMP-2, MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) [17,18].…”

Section: Introductionmentioning

confidence: 99%

Extracellular matrix in obesity – cancer interactions

Barreto¹,

Hopkins²,

Bhowmick³

et al. 2015

Hormone Molecular Biology and Clinical Investigation

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Obesity or overweight is a risk factor for several health disorders such as type 2 diabetes, hypertension, and certain cancers. Furthermore, obesity affects almost all body systems including the extracellular matrix (ECM) by generating a pro-inflammatory environment, which are associated with abnormal secretions of several cytokines or hormonal substances, for example, insulin-like growth factors (IGFs), leptin, and sex hormones. These chemical mediators most likely have a great impact on the ECM. Accumulating evidence suggests that both obesity and ECM can influence tumor growth and progression through a number of chemical mediators. Conversely, cells in the connective tissue, namely fibroblasts and macrophages, support and aggravate the inflammatory situation in obesity by releasing several cytokines or growth factors such as vascular endothelial growth factor, epidermal growth factor, and transforming growth factor-beta (TGF-β). A wide range of functions are performed by TGF-β in normal health and pathological conditions including tumorigenesis. Breast cancer in postmenopausal women is a classic example of obesity-related cancer wherein several of these conditions, for example, higher levels of pro-inflammatory cytokines, impairment in the regulation of estrogen and growth factors, and dysregulation of different ECM components may favor the neoplastic process. Aberrant expressions of ECM components such as matrix metalloproteinases or matricellular proteins in both obesity and cancer have been reported by many studies. Nonstructural matricellular proteins, viz., thrombospondins, secreted protein acidic and rich in cysteine (SPARC), and Cyr61-CTGF-Nov (CCN), which function as modulators of cell-ECM interactions, exhibit protean behavior in cancer. Precise understanding of ECM biology can provide potential therapeutic targets to combat obesity-related pathologies.

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Regulated expression of matrix metalloproteinases, inflammatory mediators, and endometrial matrix remodeling by 17beta-estradiol in the immature rat uterus

Cited by 37 publications

References 59 publications

Estrogen improves TIMP-MMP balance and collagen distribution in volume-overloaded hearts of ovariectomized females

Estrogen improves TIMP-MMP balance and collagen distribution in volume-overloaded hearts of ovariectomized females

Genome-wide gene expression analysis of peripheral leukocytes in relation to the male predominance of Guillain–Barre syndrome: differential gene expression between male and female patients

Extracellular matrix in obesity – cancer interactions

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