The connexin mimetic peptide Gap27 increases human dermal fibroblast migration in hyperglycemic and hyperinsulinemic conditions in vitro.
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The connexin mimetic peptide Gap27 increases human dermal fibroblast migration in hyperglycemic and hyperinsulinemic conditions in vitro. / Wright, Catherine S; Pollok, Simone; Flint, David J; Brandner, Johanna; Martin, Patricia E M.
In: J CELL PHYSIOL, Vol. 227, No. 1, 1, 2012, p. 77-87.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - The connexin mimetic peptide Gap27 increases human dermal fibroblast migration in hyperglycemic and hyperinsulinemic conditions in vitro.
AU - Wright, Catherine S
AU - Pollok, Simone
AU - Flint, David J
AU - Brandner, Johanna
AU - Martin, Patricia E M
PY - 2012
Y1 - 2012
N2 - Significant increases in skin wound healing rates occur by reducing connexin-mediated communication (CMC). Gap27, a connexin (Cx) mimetic peptide targeted to the second extracellular loop of Cx43, which inhibits CMC, increases migration of human keratinocytes and dermal fibroblasts. To examine the efficacy of Gap27 in a hyperglycemic and hyperinsulinemic in vitro environment, cell migration, gap junction, and Cx hemichannel functionality and cell-substrate adhesion assays were performed on human dermal fibroblasts and diabetic fibroblast and keratinocytes. To investigate fibroblast genes involved in these processes, extra-cellular matrix (ECM) and adhesion gene expression was determined with a PCR array. Gap27 increased fibroblast migration in both euglycemia/euinsulinemia and hyperglycemia/hyperinsulinemia, and influenced migration in diabetic keratinocytes. Hyperglycemia/hyperinsulinemia reduced gap junction coupling in fibroblasts and Gap27 reduced CMC and cell adhesion to substrata in fibroblasts cultured in high glucose. Migrating dermal fibroblast ECM and cell adhesion genes were found to be differentially regulated by Gap27 in euglycemia and hyperglycemia. The PCR array showed that Gap27 upregulated 34 genes and downregulated 1 gene in euglycemic migrating fibroblasts. By contrast in hyperglycemia, Gap27 upregulated 1 gene and downregulated 9 genes. In euglycemic conditions, Gap27 induced upregulation of genes associated with ECM remodeling, whereas in hyperglycemia, ECM component genes were downregulated by Gap27. Thus, Gap27 improves cell migration during scrape-wound repair in hyperglycemia/hyperinsulinemia conditions in vitro, although migration of diabetic cells is less influenced. Our results suggest that this increase in motility may occur by decreasing gap junction and hemichannel activity and altering gene expression in the adhesion and ECM pathway.
AB - Significant increases in skin wound healing rates occur by reducing connexin-mediated communication (CMC). Gap27, a connexin (Cx) mimetic peptide targeted to the second extracellular loop of Cx43, which inhibits CMC, increases migration of human keratinocytes and dermal fibroblasts. To examine the efficacy of Gap27 in a hyperglycemic and hyperinsulinemic in vitro environment, cell migration, gap junction, and Cx hemichannel functionality and cell-substrate adhesion assays were performed on human dermal fibroblasts and diabetic fibroblast and keratinocytes. To investigate fibroblast genes involved in these processes, extra-cellular matrix (ECM) and adhesion gene expression was determined with a PCR array. Gap27 increased fibroblast migration in both euglycemia/euinsulinemia and hyperglycemia/hyperinsulinemia, and influenced migration in diabetic keratinocytes. Hyperglycemia/hyperinsulinemia reduced gap junction coupling in fibroblasts and Gap27 reduced CMC and cell adhesion to substrata in fibroblasts cultured in high glucose. Migrating dermal fibroblast ECM and cell adhesion genes were found to be differentially regulated by Gap27 in euglycemia and hyperglycemia. The PCR array showed that Gap27 upregulated 34 genes and downregulated 1 gene in euglycemic migrating fibroblasts. By contrast in hyperglycemia, Gap27 upregulated 1 gene and downregulated 9 genes. In euglycemic conditions, Gap27 induced upregulation of genes associated with ECM remodeling, whereas in hyperglycemia, ECM component genes were downregulated by Gap27. Thus, Gap27 improves cell migration during scrape-wound repair in hyperglycemia/hyperinsulinemia conditions in vitro, although migration of diabetic cells is less influenced. Our results suggest that this increase in motility may occur by decreasing gap junction and hemichannel activity and altering gene expression in the adhesion and ECM pathway.
KW - Humans
KW - Cells, Cultured
KW - Oligonucleotide Array Sequence Analysis
KW - Polymerase Chain Reaction
KW - Cell Movement/physiology
KW - Gap Junctions/metabolism
KW - Cell Adhesion/physiology
KW - Gene Expression Profiling
KW - Biomimetics
KW - Connexin 43/metabolism
KW - Diabetes Mellitus, Type 2/metabolism
KW - Extracellular Matrix/metabolism
KW - Fibroblasts/cytology/metabolism
KW - Hyperglycemia/metabolism
KW - Hyperinsulinism/metabolism
KW - Keratinocytes/cytology/metabolism
KW - Skin/cytology/metabolism
KW - Wound Healing/physiology
KW - Humans
KW - Cells, Cultured
KW - Oligonucleotide Array Sequence Analysis
KW - Polymerase Chain Reaction
KW - Cell Movement/physiology
KW - Gap Junctions/metabolism
KW - Cell Adhesion/physiology
KW - Gene Expression Profiling
KW - Biomimetics
KW - Connexin 43/metabolism
KW - Diabetes Mellitus, Type 2/metabolism
KW - Extracellular Matrix/metabolism
KW - Fibroblasts/cytology/metabolism
KW - Hyperglycemia/metabolism
KW - Hyperinsulinism/metabolism
KW - Keratinocytes/cytology/metabolism
KW - Skin/cytology/metabolism
KW - Wound Healing/physiology
M3 - SCORING: Journal article
VL - 227
SP - 77
EP - 87
JO - J CELL PHYSIOL
JF - J CELL PHYSIOL
SN - 0021-9541
IS - 1
M1 - 1
ER -
