TY - JOUR
T1 - Matrix metalloproteinase-13 Is required for zebra fish (Danio rerio) development and is a target for glucocorticoids
AU - Hillegass, Jedd Michael
AU - Villano, Caren Melissa
AU - Cooper, Keith Raymond
AU - White, Lori Anne
N1 - Funding Information:
AB strain zebrafish were obtained from the ZIRC, which is supported by Grant No. RR12546 from the National Institutes of Health -National Center for Research Resources. This research was supported by the National Institute of Environmental Health Sciences (NIEHS) training grant 5T32ESO7148, the New Jersey Agricultural Experiment Station, Cook College, Rutgers University, and by the NIEHS-sponsored University of Medicine and Dentistry of New Jersey Center for Environmental Exposures and Disease, Grant No.#: NIEHS P30ES005022.
PY - 2007/11
Y1 - 2007/11
N2 - Matrix metalloproteinases (MMPs) are endopeptidases that degrade the proteins of the extracellular matrix (ECM). Expression and activity of the MMPs are essential for embryogenesis, where MMPs participate in the normal ECM remodeling that occurs during tissue morphogenesis and development. Studies have demonstrated that MMP gene expression is inhibited by glucocorticoids in mammalian cell culture systems and that exposure to glucocorticoids causes developmental abnormalities in several species. Therefore, we proposed that glucocorticoids impede normal development through alteration of MMP expression. Zebra fish (Danio rerio) were used as a model to study MMP-13 expression both during normal embryogenesis and following acute exposure to two glucocorticoids, dexamethasone, and hydrocortisone. MMP-13 is one of three collagenases identified in vertebrates that catalyzes the degradation of type I collagens at neutral pH. MMP-13 expression varied during zebra fish development, with peak expression at 48 h post-fertilization (hpf). Morpholino knockdown studies showed that MMP-13 expression is necessary for normal zebra fish embryogenesis. Acute exposure to dexamethasone and hydrocortisone resulted in abnormal zebra fish development including craniofacial abnormalities, altered somitogenesis, blood pooling and pericardial and yolk sac edema as well as increased MMP-13 mRNA and activity at 72 hpf. In situ hybridization experiments were used to confirm the increase in MMP-13 expression following glucocorticoid treatment and showed elevated MMP-13 expression in the rostral trunk, brain, eye, heart, and anterior kidney of treated embryos. These data demonstrate that normal zebra fish embryogenesis requires MMP-13 and that dexamethasone and hydrocortisone modulate the expression of this gene, leading to increased activity and potentially contributing to subsequent dysmorphogenesis.
AB - Matrix metalloproteinases (MMPs) are endopeptidases that degrade the proteins of the extracellular matrix (ECM). Expression and activity of the MMPs are essential for embryogenesis, where MMPs participate in the normal ECM remodeling that occurs during tissue morphogenesis and development. Studies have demonstrated that MMP gene expression is inhibited by glucocorticoids in mammalian cell culture systems and that exposure to glucocorticoids causes developmental abnormalities in several species. Therefore, we proposed that glucocorticoids impede normal development through alteration of MMP expression. Zebra fish (Danio rerio) were used as a model to study MMP-13 expression both during normal embryogenesis and following acute exposure to two glucocorticoids, dexamethasone, and hydrocortisone. MMP-13 is one of three collagenases identified in vertebrates that catalyzes the degradation of type I collagens at neutral pH. MMP-13 expression varied during zebra fish development, with peak expression at 48 h post-fertilization (hpf). Morpholino knockdown studies showed that MMP-13 expression is necessary for normal zebra fish embryogenesis. Acute exposure to dexamethasone and hydrocortisone resulted in abnormal zebra fish development including craniofacial abnormalities, altered somitogenesis, blood pooling and pericardial and yolk sac edema as well as increased MMP-13 mRNA and activity at 72 hpf. In situ hybridization experiments were used to confirm the increase in MMP-13 expression following glucocorticoid treatment and showed elevated MMP-13 expression in the rostral trunk, brain, eye, heart, and anterior kidney of treated embryos. These data demonstrate that normal zebra fish embryogenesis requires MMP-13 and that dexamethasone and hydrocortisone modulate the expression of this gene, leading to increased activity and potentially contributing to subsequent dysmorphogenesis.
KW - Development
KW - Glucocorticoids
KW - MMPs
KW - Matrix metalloproteinases
KW - Zebra fish
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U2 - 10.1093/toxsci/kfm192
DO - 10.1093/toxsci/kfm192
M3 - Article
C2 - 17728286
AN - SCOPUS:35448992195
SN - 1096-6080
VL - 100
SP - 168
EP - 179
JO - Toxicological Sciences
JF - Toxicological Sciences
IS - 1
ER -