High Glucose Alters Proteoglycan Expression and the Glycosaminoglycan Composition in Placentas of Women with Gestational Diabetes Mellitus and in Cultured Trophoblasts

Chen, C.-P.; Chang, Shih-Chuan; Yang, Wei

doi:10.1016/j.placenta.2006.02.009

Cited by 39 publications

(26 citation statements)

References 41 publications

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“…Known proteoglycans that can reduce levels of active TGF β 56 are expressed by bovine retinal pericytes, 47 and are upregulated by TGF β 48,57 and by hyperglycemia. 58 Decorin, in particular, is upregulated 20-fold under hyperglycemic conditions in human mesangial cells, 59,60 as are bovine retinal pericyte-associated proteoglycans. 61 …”

Section: Discussionmentioning

confidence: 99%

Glucose and TGFβ2 Modulate the Viability of Cultured Human Retinal Pericytes and Their VEGF Release

Vidro

Gee

Unda

et al. 2008

Current Eye Research

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Purpose Determine the effects of glucose and exogenous TGFβ2 on viability and VEGF release by human retinal pericytes (HRP). Methods Human retinal pericytes (HRP) were cultured in 5 mM (physiologic) or high (18 mM) glucose with or without added TGFβ2. Viable cells were counted; TGFβ2 and VEGF in the conditioned media (CM) were measured by ELISA. Results High glucose significantly reduced viable cell number and increased the levels of TGFβ2 and VEGF. TGFβ2 caused a significant dose-dependent effect on viable cell number and on the level of VEGF secreted into the CM by HRP in physiologic glucose, decreasing viable cell number, and increasing VEGF release per 1000 cells at a low concentration (0.1 ng/ml) and increasing viable cell number and decreasing VEGF release per 1000 cells at higher concentrations (1.0 and 10 ng/ml). TGFβ2 affected neither parameter in high glucose. Conclusions Elevated glucose decreased HRP viability and modulated changes in TGFβ2 and VEGF release. This suggests a novel mechanism for HRP dropout in diabetic retinopathy.

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Section: Discussionmentioning

confidence: 99%

Glucose and TGFβ2 Modulate the Viability of Cultured Human Retinal Pericytes and Their VEGF Release

Vidro

Gee

Unda

et al. 2008

Current Eye Research

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“…Biglycan and decorin are expressed in a variety of gestational tissues in humans, including the placenta [22] and fetal membranes [23], [24], [25], [26]. Biglycan is expressed in the pregnant mouse uterus [27], [28], while both biglycan and decorin are decreased in the human myometrium during labor [29].…”

Section: Introductionmentioning

confidence: 99%

Uterine Dysfunction in Biglycan and Decorin Deficient Mice Leads to Dystocia during Parturition

Aron

Macksoud

et al. 2012

PLoS ONE

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Cesarean birth rates are rising. Uterine dysfunction, the exact mechanism of which is unknown, is a common indication for Cesarean delivery. Biglycan and decorin are two small leucine-rich proteoglycans expressed in the extracellular matrix of reproductive tissues and muscle. Mice deficient in biglycan display a mild muscular dystrophy, and, along with mice deficient in decorin, are models of Ehlers-Danlos Syndrome, a connective tissue anomaly associated with uterine rupture. As a variant of Ehlers-Danlos Syndrome is caused by a genetic mutation resulting in abnormal biglycan and decorin secretion, we hypothesized that biglycan and decorin play a role in uterine function. Thus, we assessed wild-type, biglycan, decorin and double knockout pregnancies for timing of birth and uterine function. Uteri were harvested at embryonic days 12, 15 and 18. Nonpregnant uterine samples of the same genotypes were assessed for tissue failure rate and spontaneous and oxytocin-induced contractility. We discovered that biglycan/decorin mixed double-knockout dams displayed dystocia, were at increased risk of delayed labor onset, and showed increased tissue failure in a predominantly decorin-dependent manner. In vitro spontaneous uterine contractile amplitude and oxytocin-induced contractile force were decreased in all biglycan and decorin knockout genotypes compared to wild-type. Notably, we found no significant compensation between biglycan and decorin using quantitative real time PCR or immunohistochemistry. We conclude that the biglycan/decorin mixed double knockout mouse is a model of dystocia and delayed labor onset. Moreover, decorin is necessary for uterine function in a dose-dependent manner, while biglycan exhibits partial compensatory mechanisms in vivo. Thus, this model is poised for use as a model for testing novel targets for preventive or therapeutic manipulation of uterine dysfunction.

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“…They are expressed in the human placenta, where they are increased in association with gestational diabetes mellitus (Chen et al 2007). Biglycan is expressed in the pregnant mouse uterus (San Martin et al 2003, San Martin & Zorn 2003), while both biglycan and decorin are decreased in the human myometrium during labor (Hjelm et al 2002).…”

Section: Introductionmentioning

confidence: 99%

A mouse model of spontaneous preterm birth based on the genetic ablation of biglycan and decorin

Calmus¹,

Macksoud²,

Tucker³

et al. 2011

Reproduction

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Preterm premature rupture of membranes is responsible for one third of preterm births. Ehlers-Danlos syndrome (EDS) is associated with preterm premature rupture of membranes in humans. Notably, an EDS variant is caused by a genetic mutation resulting in abnormal secretion of biglycan and decorin, two small leucine-rich proteoglycans highly expressed in reproductive tissues. Because biglycan/decorin null mutant (Bgn−/−Dcn−/−) mice demonstrate phenotypic changes similar to EDS, we utilized this model to test whether either or both biglycan and decorin play a role in the attainment of successful term gestation. Wild-type, biglycan null mutant, decorin null mutant and biglycan/decorin null mutant pregnancies were assessed for length of gestation, pup and placenta weight and litter size. Quantitative real-time polymerase chain reaction was performed to measure biglycan and decorin gene expression and immunohistochemistry was performed to assess protein expression in placenta and fetal membranes at embryonic day E12, E15 and E18. Bgn−/−Dcn−/− dams displayed preterm birth, whereas the possession of at least two biglycan or decorin wild-type alleles was protective of preterm birth. Bgn−/−Dcn−/− pups were decreased at postnatal day P1 but not at E18. Biglycan and decorin were upregulated in the placenta in each other’s absence and were developmentally regulated in fetal membranes, suggesting that these two proteoglycans demonstrate genetic complementation and contribute to gestational success in a dose dependent manner. Thus, the biglycan/decorin null mutant mouse is a model of genetically induced preterm birth and perinatal loss. This model presents novel targets for preventive or therapeutic manipulation of preterm birth.

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High Glucose Alters Proteoglycan Expression and the Glycosaminoglycan Composition in Placentas of Women with Gestational Diabetes Mellitus and in Cultured Trophoblasts

Cited by 39 publications

References 41 publications

Glucose and TGFβ2 Modulate the Viability of Cultured Human Retinal Pericytes and Their VEGF Release

Glucose and TGFβ2 Modulate the Viability of Cultured Human Retinal Pericytes and Their VEGF Release

Uterine Dysfunction in Biglycan and Decorin Deficient Mice Leads to Dystocia during Parturition

A mouse model of spontaneous preterm birth based on the genetic ablation of biglycan and decorin

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