Increased expression of keratinocyte growth factor messenger RNA associated with inflammatory bowel disease

Finch, PW; Pricolo, Victor E.; Wu, Aibin; Finkelstein, SD

doi:10.1053/gast.1996.v110.pm8566591

Cited by 119 publications

(82 citation statements)

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“…In contrast, the number of cells in control samples decreased throughout time likely due to cell death. In agreement with previous studies, [15][16][17][18][19][20][21] these results suggest that in addition to promoting proliferation, KGF, P-KGF, and PL-P-KGF may also promote cell survival.…”

Section: P-kgf and Plasmin-derived P-kgf Retain Biological Activitysupporting

confidence: 93%

“…13 KGF is also important in protecting epithelial tissues from injury and apoptosis and promoting wound healing. 14 For example, KGF was strongly up-regulated in the intestines of patients suffering from bowel inflammatory disease 15,16 and protected the gut epithelium from colitis-induced inflammation. 17 Similarly, several studies showed that KGF protected the lung epithelium from hyperoxic injury 18 -21 by promoting expression of surfactant proteins, 22 secretion of surfactants, 23 and DNA repair.…”

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confidence: 99%

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Biomimetic Delivery of Keratinocyte Growth Factor upon Cellular Demand for Accelerated Wound Healing in Vitro and in Vivo

Geer

Swartz

Andreadis

2005

The American Journal of Pathology

111

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Exogenous keratinocyte growth factor (KGF) significantly enhances wound healing, but its use is hampered by a short biological half-life and lack of tissue selectivity. We used a biomimetic approach to achieve cell-controlled delivery of KGF by covalently attaching a fluorescent matrix-binding peptide that contained two domains: one recognized by factor XIII and the other by plasmin. Modified KGF was incorporated into the fibrin matrix at high concentration in a factor XIII-dependent manner. Cell-mediated activation of plasminogen to plasmin degraded the fibrin matrix and cleaved the peptides, releasing active KGF to the local microenvironment and enhancing epithelial cell proliferation and migration. To demonstrate in vivo effectiveness, we used a hybrid model of wound healing that involved transplanting human bioengineered skin onto athymic mice. At 6 weeks after grafting, the transplanted tissues underwent full thickness wounding and treatment with fibrin gels containing bound KGF. In contrast to topical KGF, fibrin-bound KGF persisted in the wounds for several days and was released gradually, resulting in significantly enhanced wound closure. A fibrinolytic inhibitor prevented this healing, indicating the requirement for cell-mediated fibrin degradation to release KGF. In conclusion, this biomimetic approach of localized, cell-controlled delivery of growth factors may accelerate healing of large full-thickness wounds and chronic wounds that are notoriously difficult to heal. Re-establishing an epithelial barrier in injured skin is a crucial wound-healing event that protects the body against further water loss and exposure to external pathogens. Skin epithelial cells or keratinocytes begin migrating to repair the epithelium ϳ18 to 24 hours after injury 1 carefully degrading a fibrin-rich clot through the activation of plasminogen into plasmin. 2 Transient interactions with extracellular matrix proteins in the wound such as collagen and fibronectin during fibrinolysis of the clot guide the keratinocytes into the wound space. Degranulating platelets are embedded in the fibrin matrix and release growth factors and cytokines, which activate keratinocytes to proliferate and migrate until they heal the defect.Keratinocyte growth factor (KGF), a member of the fibroblast growth factor family (FGF-7), plays a prominent role in epithelial morphogenesis and wound healing. 3,4 Although initial studies restricted expression of KGF in cells of mesenchymal origin, 5,6 a recent study documented expression of KGF by dendritic epidermal T cells of the skin immediately after wounding, 7 suggesting that KGF may play an important role in epidermal immunity. The paracrine action of KGF on epithelial cells is mediated through the KGF receptor (KGFR or FGFR2IIIb), a splice variant of FGF-2 receptor encoded by the gene fgfr-2. 8,9 KGF is thought to be an important player in development and morphogenesis of epithelial tissues and a promoter of mesenchymal-epithelial interactions. 10,11 Targeting KGF expression to the basal keratinocyt...

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Section: P-kgf and Plasmin-derived P-kgf Retain Biological Activitysupporting

confidence: 93%

mentioning

confidence: 99%

Biomimetic Delivery of Keratinocyte Growth Factor upon Cellular Demand for Accelerated Wound Healing in Vitro and in Vivo

Geer

Swartz

Andreadis

2005

The American Journal of Pathology

111

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“…Indeed, our laboratory and others demonstrated a strong upregulation of KGF expression after injury to murine and human skin (Werner et al, 1992;Marchese et al, 1995) and also to other tissues (reviewed by Werner, 1998). Furthermore, expression of KGF was shown to be increased in human in¯ammatory diseases, such as psoriasis (Finch et al, 1997) and in¯ammatory bowel disease Finch et al, 1996). These results suggest that KGF stimulates proliferation and/or migration of epithelial cells in injured and in¯amed tissues, a hypothesis which was supported by inhibition of wound re-epithelialization in transgenic mice expressing a dominant-negative KGF receptor in the epidermis (Werner et al, 1994).…”

Section: Introductionmentioning

confidence: 91%

Growth factor – regulated expression of enzymes involved in nucleotide biosynthesis: a novel mechanism of growth factor action

1999

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Keratinocyte growth factor (KGF) is a potent and speci®c mitogen for epithelial cells, including the keratinocytes of the skin. We investigated the mechanisms of action of KGF by searching for genes which are regulated by this growth factor in cultured human keratinocytes. Using the di erential display RT ± PCR technology we identi®ed the gene encoding adenylosuccinate lyase [EC 4.3 [EC 3.5.2.3]). Expression of all of these enzymes was upregulated after treatment with KGF and also with epidermal growth factor (EGF), indicating that these mitogens stimulate nucleotide production by induction of these enzymes. To determine a possible in vivo correlation between the expression of KGF, EGF and the enzymes mentioned above, we analysed the expression of the enzymes during cutaneous wound repair, where high levels of these mitogens are present. Indeed, we found a strong mRNA expression of all of these enzymes in the EGF-and KGF-responsive keratinocytes of the hyperproliferative epithelium at the wound edge, indicating that their expression might also be regulated by growth factors during wound healing.

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“…Furthermore, rKGF promote skin, lung, and intestinal tissue regeneration in model systems of injury (15,16,18,19). Supporting a role for KGF in tissue repair, both KGF and KGFR are overexpressed in intestinal tissues obtained from inflammatory bowel disease (IBD) patients (20,21). The cellular origin of KGF in human IBD remains ambiguous but fibroblasts and T lymphocytes were identified as judged from an analysis of the topographic distribution of these cells and KGF mRNA (20).…”

mentioning

confidence: 99%

“…Supporting a role for KGF in tissue repair, both KGF and KGFR are overexpressed in intestinal tissues obtained from inflammatory bowel disease (IBD) patients (20,21). The cellular origin of KGF in human IBD remains ambiguous but fibroblasts and T lymphocytes were identified as judged from an analysis of the topographic distribution of these cells and KGF mRNA (20). These data suggest that KGF is an important growth factor to help maintain and͞or restore the integrity of epithelial tissues after injury.…”

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confidence: 99%

Protection of the intestinal mucosa by intraepithelial γδ T cells

Chen

Chou

Fuchs

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

436

371

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Increased expression of keratinocyte growth factor messenger RNA associated with inflammatory bowel disease

Cited by 119 publications

References 1 publication

Biomimetic Delivery of Keratinocyte Growth Factor upon Cellular Demand for Accelerated Wound Healing in Vitro and in Vivo

Biomimetic Delivery of Keratinocyte Growth Factor upon Cellular Demand for Accelerated Wound Healing in Vitro and in Vivo

Growth factor – regulated expression of enzymes involved in nucleotide biosynthesis: a novel mechanism of growth factor action

Protection of the intestinal mucosa by intraepithelial γδ T cells

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