Age-related changes in alpha 1- and alpha 2-chain type IV collagen mRNAs in adult mouse glomeruli: competitive PCR

Peten, Emmanuel P.; García-Peréz, A.; Terada, Yoshio; Woodrow, David; Martin, Brian M.; Striker, Gary E.; Striker, Liliane J.

doi:10.1152/ajprenal.1992.263.5.f951

Cited by 41 publications

(61 citation statements)

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“…MMPs and their tissue inhibitors play a central role in the pathogenesis of deposit accumulation in multiple disorders such as renal disease and atherosclerosis (Belkhiri et al, 1997;Dollery and Libby, 2006;Peten et al, 1992). Aging and AMD eyes accumulate extracellular deposits under the RPE and within Bruch's membrane, and are in part due to dysregulation of ECM.…”

Section: Discussionmentioning

confidence: 99%

Subtype specific estrogen receptor action protects against changes in MMP-2 activation in mouse retinal pigmented epithelial cells

Elliot

Catanuto

Fernández

et al. 2008

Experimental Eye Research

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Eyes with age-related macular degeneration (AMD) demonstrate accumulation of specific deposits and extracellular matrix (ECM) molecules under the retinal pigment epithelium (RPE). AMD is about two times more prevalent in aging postmenopausal women. Therefore we studied whether 17β-estradiol (E 2 ) modulates the expression and activity of the trimolecular complex (MMP-2, TIMP-2 and MMP-14), molecules which are of major importance for ECM turnover in RPE. We used cell lines isolated from estrogen receptor knockout mice (ERKO) to determine which ER (estrogen receptor) subtype was important for ECM regulation in RPE cells.We found that mouse RPE sheets had higher baseline MMP-2 activity in the presence of ERβ. This correlated with higher MMP-2 activity in RPE cell lines isolated from ERKOα mice. Exposure to E 2 increased MMP-2 activity in mouse RPE cell lines. In addition E 2 increased transcriptional activation of the MMP-2 promoter through a functional Sp1 site which required the presence of ERβ, but not ERα. E 2 also maintained levels of pro MMP-2, and MMP-14 and TIMP-2 activity after oxidant injury. Since the direct effects of E 2 on MMP-2 transcriptional activation and the regulation of the trimolecular complex after oxidant induced injury requires ERβ, this receptor subtype may have a role as a potential therapeutic target to prevent changes in activation of MMP-2.

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Section: Discussionmentioning

confidence: 99%

Subtype specific estrogen receptor action protects against changes in MMP-2 activation in mouse retinal pigmented epithelial cells

Elliot

Catanuto

Fernández

et al. 2008

Experimental Eye Research

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“…13 MCs were identified by their morphology and positive staining with an antibody to ␣-smooth muscle cell actin. Cell culture experiments were performed on cells between passages 3 to 10.…”

Section: Cell Culturementioning

confidence: 99%

Differential Effects of Continuous and Intermittent 17β-Estradiol Replacement and Tamoxifen Therapy on the Prevention of Glomerulosclerosis

Karl

Berho

Pignac-Kobinger

et al. 2006

The American Journal of Pathology

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Female ROP Os/؉ mice are partially protected by endogenous estrogens against progressive glomerulosclerosis (GS) during their reproductive period; however, ovariectomy accelerates GS progression. We examined the effects of continuous and intermittent 17␤-estradiol (E 2 ) replacement and tamoxifen therapy on the development of GS in ovariectomized (Ovx) ROP Os/؉ mice. Continuous E 2 replacement (CE 2 ) throughout 9 months prevented microalbuminuria and excess extracellular matrix accumulation in Ovx ROP Os/؉, not only compared to placebo-treated Ovx mice but also in comparison to intact female ROP Os/؉. Tamoxifen had a similar effect, but of lesser magnitude. Intermittent 3-month on-off-on E 2 did not reduce the kidney changes. Mesangial cells (MCs) from CE 2 mice maintained their estrogen responsiveness. E 2 in vitro prevented transforming growth factor-␤1 stimulation of a Smad-responsive reporter construct and increased MMP-2 expression and activity in MCs isolated from CE 2 mice. MCs from mice on either placebo or intermittent E 2 treatment did not respond to added E 2 , consistent with a stable alteration of their estrogen responsiveness. Tamoxifen protection against GS was less pronounced in ROP Os/؉ mice. Thus, prolonged estrogen deficiency promotes GS and renders MCs insensitive to subsequent estrogen treatment. This underscores the importance of continuous estrogen exposure for maintaining glomerular function and structure in females susceptible to progressive GS. The glomerulus is a direct estrogen target tissue that predominantly expresses the estrogen receptor (ER) subtype ␣.1 Estrogens regulate genes involved in extracellular matrix (ECM) turnover in a manner leading to the prevention of the accumulation of ECM in the mesangium in mouse strains that do not develop glomerulosclerosis (GS) in response to renal injuries such as nephron reduction or experimentally induced diabetes (sclerosis-resistant mouse models). [1][2][3][4][5] In comparison, the level of glomerular ER expression is inversely correlated with the susceptibility to GS among different mouse strains.3 Furthermore, in other rodent models estrogen replacement therapy has also been shown to decrease glomerular damage in uninephrectomized, spontaneously hypertensive rats, to attenuate GS in aging Dahl salt-sensitive rats, and to normalize the decreased renal functional reserve in ovariectomized (Ovx) Wistar rats. 6 -8 Female ROP Os/ϩ mice develop GS during their reproductive period of life and are, therefore, considered sclerosis-prone. 9 However, estrogen deficiency, induced by ovariectomy, accelerates glomerular dysfunction and scarring in young ROP Os/ϩ mice. 9 This suggests that endogenous estrogens only partially protect this mouse strain from the development of GS. Thus, female ROP Os/ϩ mice represent a model of progressive GS that specifically resembles those women who develop chronic kidney disease (CKD) in midlife with rapidly deteriorating kidney function after the onset of menopause.To address the question of the efficacy of est...

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“…17 Amplification and quantification of target RNAs was performed on an ABI PRISM 7700 Sequence Detection System (Applied Biosystems, Foster City, CA). 6 TaqMan probes and primers for amplification of the specific transcripts were designed using the Primer Express 1.5 from Applied Biosystems.…”

Section: Isolation Of Rna and Quantitative Analysis Of Rna Expressionmentioning

confidence: 99%

Estrogen Deficiency Accelerates Progression of Glomerulosclerosis in Susceptible Mice

Elliot¹,

Karl²,

Berho³

et al. 2003

The American Journal of Pathology

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Estrogen deficiency may contribute to the development and progression of glomerulosclerosis in postmenopausal women. The responsiveness to estrogens could be controlled by genetic traits related to those that determine the susceptibility to glomerular scarring. This study was undertaken to determine whether the intensity of the sclerotic response was modified by the estrogen status in sclerosis-prone ROP Os/؉ mice. Ovariectomized ROP Os/؉ mice developed more severe renal dysfunction and glomerulosclerosis than intact, ie, estrogen sufficient agematched female mice. Ovariectomized ROP Os/؉ exhibited increased accumulation of extracellular matrix, predominantly of laminin, and a marked distortion of the glomerular architecture. We found an increase in macrophage infiltration in the mesangium of ovariectomized ROP Os/؉. Estrogen deficiency decreased glomerular estrogen receptor expression in ROP Os/؉ mice, which we had previously found to be low in the parental ROP strain. Thus, although physiological estrogen levels in young ROP Os/؉ mice could not prevent the development of glomerulosclerosis, estrogen deficiency accelerated the progression of glomerular scarring in this mouse strain. This suggests that estrogen replacement will slow but not prevent the progression of glomerulosclerosis. It underscores the importance of the genetic composition of individuals that determines the susceptibility to diseases as well as the response to treatment. Estrogen deficiency may contribute to the development and progression of glomerulosclerosis in postmenopausal women. This is suggested by data from the United States Renal Data System, which show that the female to male ratio of patients with end-stage renal disease because of diabetes increases sharply in the postmenopausal age groups, especially of those from ethnic minorities. 1 The United States Renal Data System data as well as additional genetic and epidemiological studies also suggest that genetic factors play an important role in the susceptibility to develop glomerulosclerosis and the progression to end-stage renal disease. 2,3 The responsiveness to estrogens, which is primarily determined by the level of estrogen receptor (ER) expression, 4 could be controlled by genetic traits related to those that determine the susceptibility to glomerular scarring. We have previously shown that the renal glomerulus is a direct target tissue for estrogens. 5,6 Human and mouse mesangial cells, which play a central role in the pathogenesis of glomerulosclerosis, express both ER subtypes ␣ and ␤. 5 We reported that these ERs were transcriptionally active and that estrogens positively regulated ER expression in mesangial cells. 5 We also found that estrogens provided protection from glomerulosclerosis by regulating genes involved in extracellular matrix (ECM) turnover in a manner leading to the prevention of ECM accumulation in the mesangium. 5,6 Estrogen treatment increased the expression and activity of matrix metalloproteinase (MMP)-9 in mesangial cells isolated from glomeruloscler...

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Age-related changes in alpha 1- and alpha 2-chain type IV collagen mRNAs in adult mouse glomeruli: competitive PCR

Cited by 41 publications

References 0 publications

Subtype specific estrogen receptor action protects against changes in MMP-2 activation in mouse retinal pigmented epithelial cells

Subtype specific estrogen receptor action protects against changes in MMP-2 activation in mouse retinal pigmented epithelial cells

Differential Effects of Continuous and Intermittent 17β-Estradiol Replacement and Tamoxifen Therapy on the Prevention of Glomerulosclerosis

Estrogen Deficiency Accelerates Progression of Glomerulosclerosis in Susceptible Mice

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