Regulation of Tissue Injury Responses by the Exposure of Matricryptic Sites within Extracellular Matrix Molecules

Davis, George E.; Bayless, Kayla J.; Davis, Michael J.; Meininger, Gerald A.

doi:10.1016/s0002-9440(10)65020-1

Cited by 406 publications

(390 citation statements)

References 102 publications

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“…The continuous conversion of soluble fibronectin into ECM fibrils occurs through a dynamic, yet tightly controlled, cell-dependent process (22). As the ECM is assembled and remodeled, changes in the conformation of matrix proteins may expose biologically active, "matricryptic" sites (8). Our studies indicate that the ECM form of fibronectin triggers changes in cytoskeletal organization that are distinct from those of soluble fibronectin (15).…”

mentioning

confidence: 78%

Fibronectin matrix polymerization regulates small airway epithelial cell migration

Hocking

Chang

2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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The continuous conversion of soluble fibronectin into extracellular matrix fibrils occurs through a dynamic, cell-dependent process. As the extracellular matrix is assembled, changes in the conformation of matrix proteins may expose biologically active, matricryptic sites that alter cell behavior. In this study, an in vitro model of wound healing was used to determine the role of matrix fibronectin in airway epithelial cell motility. Our findings indicate that, under basal conditions, small airway epithelial cell (SAEC) migration requires active fibronectin matrix polymerization. Furthermore, SAEC migration is increased significantly by the interaction of cells with a recombinant construct containing fibronectin's matricryptic III-1 site. In contrast, addition of increasing amounts of fibronectin to SAECs significantly decreased the rate of cell migration. This fibronectin-induced inhibition of cell migration was overcome by blocking excess fibronectin matrix deposition. These data indicate that SAEC migration is regulated in a biphasic manner by the polymerization of fibronectin in the extracellular matrix and suggest a stimulatory role for fibronectin's matricryptic III-1 site in cell motility.

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mentioning

confidence: 78%

Fibronectin matrix polymerization regulates small airway epithelial cell migration

Hocking

Chang

2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…[44][45][46] MMPs release soluble bioactive factors through ECM degradation and regulate macrophage chemoattractant and leukocyte infiltration during injury. MMP-13 may activate MMP-2, which in turn is able to activate chemokines CCl-7 and CXCl-12.…”

Section: Discussionmentioning

confidence: 99%

Loss of MMP 13 attenuates murine hepatic injury and fibrosis during cholestasis

et al. 2006

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“…Of note, many of the endogenous inhibitors of angiogenesis are cryptic modules within liver-specific plasma proteins. Thus, endostatin 1,5 angiostatin, 28 the cleaved form of antithrombin, 29 the kringle-2 domain of prothrombin, 30 and the domain 5 of kininogen 31 are proteolytically derived from plasma proteins that may provide tissues with cryptic signals locally activated by the tissue microenvironment, a family of proteins known as "matricryptins" 32 or "matricellular proteins." 33,34 Characterization of the tissue and circulating forms of these macromolecules may provide a better understanding of the homeostatic regulation of angiogenesis and may lead to potential diagnostic applications.…”

Section: Discussionmentioning

confidence: 99%

Tumor Hepatocytes and Basement Membrane-Producing Cells Specifically Express Two Different Forms of the Endostatin Precursor, Collagen Xviii, in Human Liver Cancers

et al. 2001

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Endostatin is an endogenous inhibitor of angiogenesis and tumor growth in mice, which may be generated by proteolytic cleavage of collagen XVIII. In normal tissues, 2 variants of the endostatin precursor, namely the SHORT and LONG forms, regulate tissue specificity. We analyzed 53 human liver biopsies (18 hepatocellular carcinomas, 16 metastases of colorectal cancer, 3 cholangiocarcinomas, and 16 controls) by RNA dot blots, double-labeling immunohistochemistry, and in situ hybridization, using common and variant-specific probes. Tumor hepatocytes expressed the LONG form, whereas cholangiocarcinoma cells expressed the SHORT form, which was deposited in tumor basement membranes. Metastatic colorectal carcinoma cells did not express collagen XVIII. In the stromal compartment of primary and metastatic cancers, myofibroblasts and vascular endothelial cells expressed the SHORT form. Both basement membrane components, collagen IV and the SHORT collagen XVIII form, were codistributed and their mRNA levels strongly correlated (R ‫؍‬ .75, P < .001). In addition, freshly isolated human hepatocytes expressed the LONG form and culture-activated stellate cells the SHORT form. Moreover, the full-length LONG form is a plasma protein. Thus, the LONG form is a hepatocyte-specific variant, and the SHORT form is a major component of the tumor extracellular matrix in primary and metastatic liver cancers. Collagen XVIII is the precursor of endostatin, an angiogenesis inhibitor that suppresses tumor growth in murine models. 1,2 It is a component of most epithelial and vascular basement membranes [3][4][5] and is expressed at high levels by human hepatocytes in normal and fibrotic livers. 6 In normal human tissues, 2 forms of collagen XVIII, respectively designated the SHORT and LONG variants, are differentially expressed: the SHORT form is ubiquitously found in basement membranes 3 ; the LONG form is almost exclusively found in the liver, expressed at remarkably high levels by normal human hepatocytes, 6,7 and regulated by liver-enriched transcription factors in similarity with other liver-specific genes. 8 The SHORT and LONG forms of collagen XVIII originate from 2 alternate promoters and have amino-terminal noncollagenous domains of 303 and 493 amino acids (Fig. 1). However, they share all the downstream sequences, including the 312-amino acid C-terminal noncollagenous domain containing the angiogenesis inhibitor, endostatin. 7 Malignant tumors may generate endostatin by proteolytic cleavage of the C-terminal domain of collagen XVIII. 5,9,10 However, the presence of the endostatin precursor, collagen XVIII, in the extracellular matrix of tumors remains to be demonstrated. We have shown that hepatocytes express high and stable levels of collagen XVIII in normal liver, active and quiescent fibrosis, 6 and small hepatocellular carcinomas, 11 whereas liver myofibroblasts increase their collagen XVIII expression by 13-fold in active liver fibrogenesis. 6 We thus hypothesized that hepatocytes and activated stellate cells may express diffe...

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Regulation of Tissue Injury Responses by the Exposure of Matricryptic Sites within Extracellular Matrix Molecules

Cited by 406 publications

References 102 publications

Fibronectin matrix polymerization regulates small airway epithelial cell migration

Fibronectin matrix polymerization regulates small airway epithelial cell migration

Loss of MMP 13 attenuates murine hepatic injury and fibrosis during cholestasis

Tumor Hepatocytes and Basement Membrane-Producing Cells Specifically Express Two Different Forms of the Endostatin Precursor, Collagen Xviii, in Human Liver Cancers

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