Matrix Metalloproteinase Activity is an Important Mediator of Cardiac Neural Crest Cell Migration

dc.contributor.advisorBrauer, Philip R.en_US
dc.contributor.authorCai, Dong Hongen_US
dc.contributor.cuauthorCai, Dong Hongen_US
dc.date.accessioned2014-12-18T17:07:12Z
dc.date.available2014-12-18T17:07:12Z
dc.date.issued2001-12en_US
dc.degree.committeeYee, John A.en_US
dc.degree.committeeMackin, Robert B.en_US
dc.degree.committeeScofield, Margaret A.en_US
dc.degree.disciplineBiomedical Sciences (graduate program)en_US
dc.degree.grantorGraduate Schoolen_US
dc.degree.levelPhD (Doctor of Philosophy)en_US
dc.degree.namePh.D. in Biomedical Sciencesen_US
dc.description.abstractMatrix metalloproteinases (MMPs) are a family of zinc proteolytic enzymes important in embryonic development and pathological processes. Cardiac neural crest (CNC) cells are derived from the dorsal portion of neural tube through an epithehal-to - mesenchymal cell transition and then migrate along the basement membrane of ectoderm, enter the pharyngeal arches, and subsequently participate in the septation of the heart during embryonic development. My studies showed that one of the MMPs, MMP-2 (gelatinase A, or 72 kDa type IV collagenase), was deposited in CNC migration pathway and was expressed by CNC cells after they entered the pharyngeal arches. Furthermore, the distribution pattern of MMP-2 was disrupted by migrating CNC cells. This suggested that MMP enzymatic activity might play an important role in CNC migration. To test this hypothesis, a synthetic MMP inhibitor KB8301 was injected into the cell-free space adjacent to the premigratory CNC cells. The distance that CNC migrated in the injected side was significantly decreased compared with that in the noninjected side and in the vehicle treated embryos. Enzyme activity assays showed that the activity of MMPs decreased about 30% after KB8301 injection. This demonstrated that enzymatic activity of MMPs is an important mediator for CNC migration. The natural inhibitors of MMPs, TIMPs, were also studied. TIMP-2, which not only has the inhibitory activity against MMPs, but also participates in the activation of proMMP-2, was expressed exclusively in a subpopulation of CNC cells during their early migration. Local delivery of exogenous TIMP-2 significantly decreased CNC migratory distance as well as MMP activity in vivo. The pattern of TIMP-3 expression suggests that this inhibitor is not likely to have a role in early NC migration but could be involved in pharyngeal arch and cardiac. Overall, my studies support the hypothesis that MMP activity is an important mediator of CNC cell migration.en_US
dc.description.noteProQuest Traditional Publishing Optionen_US
dc.description.pagesxi, 141 pagesen_US
dc.identifier.urihttp://hdl.handle.net/10504/65336
dc.language.isoen_USen_US
dc.publisherCreighton Universityen_US
dc.publisher.locationOmaha, Nebraskaen_US
dc.rightsCopyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above.en_US
dc.rights.holderDong Hong Caien_US
dc.subject.meshHeart--embryologyen_US
dc.subject.meshNeural Crest--embryologyen_US
dc.titleMatrix Metalloproteinase Activity is an Important Mediator of Cardiac Neural Crest Cell Migrationen_US
dc.typeDissertation
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