Impaired Wound Contraction in Stromelysin-1–Deficient Mice

Bullard, Kelli M.; Lund, Leif R.; Mudgett, John S.; Mellin, T.N.; Hunt, Thomas K.; Murphy, Beth S; Ronan, John; Werb, Zena; Banda, Michael J.

doi:10.1097/00000658-199908000-00017

Cited by 202 publications

(158 citation statements)

References 31 publications

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“…This convincingly agrees with observations that keratinocytes from K5-Cre:STAT3flox/-transgenic mice show impaired mobility and migration in vivo and in vitro [39]. MMP3, a protease with a wide range of substrate specificities, degrades old multicellular actin networks thereby playing a role in wound contraction [40]. Temporal degradation of the extracellular matrix seems to also be important for antimicrobial defense, as MMP3-deficient mice show reduced migration of immune cells to the site of inflammation, which is associated with a delayed clearance of bacteria [41].…”

Section: Discussionsupporting

confidence: 90%

IL‐22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis

et al. 2006

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IL‐22 is an IFN–IL‐10 cytokine family member, which is produced by activated Th1 and NK cells and acts primarily on epithelial cells. Here we demonstrate that IL‐22, in contrast to its relative IFN‐γ, regulates the expression of only a few genes in keratinocytes. This is due to varied signal transduction. Gene expressions regulated by IL‐22 should enhance antimicrobial defense [psoriasin (S100A7), calgranulin A (S100A8), calgranulin B (S100A9)], inhibit cellular differentiation (e.g., profilaggrin, keratins 1 and 10, kallikrein 7), and increase cellular mobility [e.g., matrix metalloproteinease 1 (MMP1, collagenase 1), MMP3 (stromelysin 1), desmocollin 1]. In contrast, IFN‐γ favored the expression of MHC pathway molecules, adhesion molecules, cytokines, chemokines, and their receptors. The IL‐22 effects were transcriptional and either independent of protein synthesis and secretion, or mediated by a secreted protein. Inflammatory conditions, but not keratinocyte differentiation, amplified the IL‐22 effects. IL‐22 application in mice enhanced cutaneous S100A9 and MMP1 expression. High IL‐22 levels in psoriatic skin were associated with strongly up‐regulated cutaneous S100A7, S100A8, S100A9, and MMP1 expression. Psoriatic patients showed strongly elevated IL‐22 plasma levels, which correlated with the disease severity. Expression of IL‐22 and IL‐22‐regulated genes was reduced by anti‐psoriatic therapy. In summary, despite similarities, IFN‐γ primarily amplifies inflammation, while IL‐22 may be important in the innate immunity and reorganization of epithelia.

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Section: Discussionsupporting

confidence: 90%

IL‐22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis

et al. 2006

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“…Physiologically, MMP-3 expression was negligible in normal skin but was observed in keratinocytes after injury (7). Additionally, mice that lacked MMP-3 demonstrated impaired skin healing due to inadequate wound contraction but not keratinocyte migration (8). In support with this notion, our gene silencing experiment indicated that MMP-3 has limited effect on keratinocyte migration in our experimental condition.…”

Section: Discussionsupporting

confidence: 74%

High‐glucose‐cultivated peripheral blood mononuclear cells impaired keratinocyte function via reduced IL‐22 expression: implications on impaired diabetic wound healing

Huang

Chao

et al. 2015

Experimental Dermatology

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“…In wounded Mmp7-mutant mice, epithelial cells do not migrate and E-cadherin cleavage does not occur 85 . MMP3 also functions in epidermal wound healing, as skin wounds of Mmp3-mutant mice heal more slowly than those of control mice, owing to a deficit in actin purse-string formation 86 .…”

Section: Mmp7 Is Involved In Innate Immunity and Wound Healingmentioning

confidence: 99%

Matrix metalloproteinases and the regulation of tissue remodelling

Page-McCaw

Ewald

Werb

2007

Nat Rev Mol Cell Biol

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2,589

2,180

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Matrix metalloproteinases (MMPs) were discovered because of their role in amphibian metamorphosis, yet they have attracted more attention because of their roles in disease. Despite intensive scrutiny in vitro, in cell culture and in animal models, the normal physiological roles of these extracellular proteases have been elusive. Recent studies in mice and flies point to essential roles of MMPs as mediators of change and physical adaptation in tissues, whether developmentally regulated, environmentally induced or disease associated.The founding member of the matrix metalloproteinase (MMP) family, collagenase, was identified in 1962 by Gross and Lapiere, who found that tadpole tails during metamorphosis contained an enzyme that could degrade fibrillar collagen 1,2 . Subsequently, an interstitial collagenase, collagenase-1 or MMP1, was found in diseased skin and synovium 3 . In vitro, MMP1 initiates degradation of native fibrillar collagens, crucial components of vertebrate extracellular matrix (ECM), by cleaving the peptide bond between Gly775-Ile776 or Gly775-Lys776 in native type I, II or III collagen molecules 3,4 . Further research led to the discovery of a family of structurally related proteinases (23 in human, 24 in mice), now referred to as the MMP family.Interest in MMPs increased in the late 1960s and early 1970s following observations that MMPs are upregulated in diverse human diseases including rheumatoid arthritis and cancer. Importantly, high levels of MMPs often correlated with poor prognosis in human patients (reviewed in REF. 5 ). However, recent clinical data indicate that the relationship between § These authors contributed equally to this paper. Competing interests statementThe authors declare no competing financial interests. DATABASESThe following terms in this article are linked online to: Entrez Genome: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene DmMmp1 | DmMmp2 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptMMPs and disease is not simple; for example, increased MMP activity can enhance tumour progression or can inhibit it (reviewed in REF. 6 ). This complex relationship between MMP expression and cancer has increased the basic and clinical interest in understanding MMP function in vivo, but it has also focused attention on MMPs and pathology, and relatively less attention has been focused on the normal roles of these enzymes. MMP proteolysisMMPs are members of the metzincin group of proteases, which are named after the zinc ion and the conserved Met residue at the active site 11,12 . Recent work has generated a unified peptidase nomenclature 13 Functions of MMP proteolysisHistorically, MMPs were thought to function mainly as enzymes that degrade structural components of the ECM. However, MMP proteolysis can create space for cells to migrate, can produce specific substrate-cleavage fragments with independent biological activity, can MMPs in bone modelling and remodellingBone is an important site of ongoing tissue remodelling during development...

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Impaired Wound Contraction in Stromelysin-1–Deficient Mice

Cited by 202 publications

References 31 publications

IL‐22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis

IL‐22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis

High‐glucose‐cultivated peripheral blood mononuclear cells impaired keratinocyte function via reduced IL‐22 expression: implications on impaired diabetic wound healing

Matrix metalloproteinases and the regulation of tissue remodelling

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