title: Matrix metalloproteinases 2 and 9 are dispensable for pancreatic islet formation and function in vivo.
abstract: Pancreatic islet formation is a highly regulated process that is initiated at the end of gestation in rodents. Endocrine precursor cells first form within the epithelium of duct-like structures and then delaminate from the epithelium, migrate, and cluster during the early stages of islet formation. The molecular mechanisms that regulate endocrine cell migration and islet formation are not well understood. Cell culture studies suggest that matrix metalloproteinases (MMPs) 2 and 9 are required for islet formation. To address whether MMP2 and MMP9 function are essential for endocrine cell migration and islet formation in vivo, we analyzed pancreas development in MMP2/MMP9 double-deficient mice. Our results show that islet architecture and function are unperturbed in these knockout mice, demonstrating that both MMP2 and MMP9 functions are dispensable for islet formation and endocrine cell differentiation. Our studies also show that a number of other MMPs are expressed at the time islet formation is initiated. This observation suggests that other MMPs may substitute for MMP2 and MMP9 loss in pancreatic tissue. However, islet formation is unaffected in transgenic mice with modified tissue inhibitor of metalloproteinase-1 (TIMP1) levels, suggesting that MMP activity may contribute little to islet morphogenesis in vivo.
authors.affiliation: Diabetes Center, Department of Medicine, University of California, San Francisco, California, 94143-0573, USA.
authors.forename: Sabina E
authors.initials: SE
authors.lastname: Perez
authors.forename: David A
authors.initials: DA
authors.lastname: Cano
authors.forename: Trang
authors.initials: T
authors.lastname: Dao-Pick
authors.forename: Jean-Phillipe
authors.initials: JP
authors.lastname: Rougier
authors.forename: Zena
authors.initials: Z
authors.lastname: Werb
authors.forename: Matthias
authors.initials: M
authors.lastname: Hebrok
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D015870:Gene Expression; D007515:Islets of Langerhans / Q000502:physiology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
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