title: Modulatory effects of connexin-43 expression on gap junction intercellular communications with mast cells and fibroblasts.
abstract: The influence of mast cells upon aberrant wound repair and excessive fibrosis has supportive evidence, but the mechanism for these mast cell activities is unclear. It is proposed that heterocellular gap junction intercellular communication (GJIC) between fibroblasts and mast cells directs some fibroblast activities. An in vitro model was used employing a rodent derived peritoneal mast cell line (RMC-1) and human dermal derived fibroblasts. The influence of the expression of the gap junction channel structural protein, connexin 43 (Cx-43) on heterocellular GJIC, the expression of microtubule β-tubulin and microfilament α smooth muscle actin (SMA) were investigated. The knockdown of Cx-43 by siRNA in RMC-1 cells completely blocked GJIC between RMC-1 cells. SiRNA knockdown of Cx-43 within fibroblasts only dampened GJIC between fibroblasts. It appears Cx-43 is the only expressed connexin (Cx) in RMC-1 cells. Fibroblasts express other Cxs that participate in GJIC between fibroblasts in the absence of Cx-43 expression. Heterocellular GJIC between RMC-1 cells and fibroblasts transformed fibroblasts into myofibroblasts, expressing α SMA within cytoplasmic stress fibers. The knockdown of Cx-43 in RMC-1 cells increased β-tubulin expression, but its knockdown in fibroblasts reduced β-tubulin expression. Knocking down the expression of Cx-43 in fibroblasts limited αSMA expression. Cx-43 participation is critical for heterocellular GJIC between mast cells and fibroblasts, which may herald a novel direction for controlling fibrosis.
authors.affiliation: Division of Plastic Surgery, Department of Surgery, Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033, USA.
authors.forename: Ashley L
authors.initials: AL
authors.lastname: Pistorio
authors.forename: H Paul
authors.initials: HP
authors.lastname: Ehrlich
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D018929:Cell Culture Techniques; D018031:Connexin 43 / Q000235:genetics / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D005355:Fibrosis; D017629:Gap Junctions / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D007627:Keloid / Q000235:genetics / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D014404:Tubulin / Q000235:genetics / Q000502:physiology; D014947:Wounds and Injuries / Q000235:genetics / Q000473:pathology
chemical_list: D000199:Actins; D018031:Connexin 43; D034741:RNA, Small Interfering; D014404:Tubulin; C498862:Acta2 protein, rat