Through Gap Junction Communications, Co-Cultured Mast Cells and Fibroblasts Generate Fibroblast Activities Allied with Hypertrophic Scarring

Hershey, Pa. From the Division of Plastic Surgery, Department of Surgery, Pennsylvania State University, College of Medicine.
Plastic and Reconstructive Surgery (Impact Factor: 2.99). 05/2013; 131(5):1036-44. DOI: 10.1097/PRS.0b013e3182865c3f
Source: PubMed


: The prominent inflammatory cell identified in excessive scarring is the mast cell. Hypertrophic scar exhibits myofibroblasts derived from the transformation of fibroblasts, increased collagen synthesis, and stationary nonmigratory resident cells. The co-culture of fibroblasts with an established rat mast cell line (RMC-1) was used to explore the hypothesis of whether mast cells through gap junctional intercellular communications guide fibroblasts in promoting excessive scarring.
: Human dermal fibroblasts were cultured alone or co-cultured with RMC-1 cells as is or with either blocked gap junctional intercellular communications or devoid of cytoplasmic granules. Collagen synthesis was analyzed by dot blot analysis; immunohistology identified myofibroblasts, and a cell migration assay measured fibroblast locomotion.
: Fibroblasts co-cultured with RMC-1 cells transformed into myofibroblasts, had increased collagen synthesis, and showed retarded cell migration. In contrast, RMC-1 cells unable to form gap junctional intercellular communications were similar to fibroblasts alone, failing to promote these activities. Degranulated RMC-1 cells were as effective as intact RMC-1 cells.
: Mast cells induce fibroblast activities associated with hypertrophic scarring through gap junctional intercellular communications. Eliminating the mast cell or its gap junctional intercellular communications with fibroblasts may be a possible approach in preventing hypertrophic scarring or reducing fibrotic conditions.

1 Follower
31 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: The repair of wounds usually terminates with a scar. The healing from a severe tissue loss can create a new clinical problem, excessive scarring. Approaches to prevent excessive scarring will optimize the repair process. Controlling gap-junction communications between cells and/or the transport of the proteins that form gap junctions offers new approaches for controlling this problem. Gap-junctional intercellular communication (GJIC) requires hemichannels, connexon structures, embedded in the plasma membrane of coupled cells. The connexon is composed of six proteins from the connexin (Cx) family. The docking of connexons between the neighboring cells forms a gated channel, where small molecules can pass directly between the cytoplasm of cells. In wound repair, GJIC between fibroblasts in granulation tissue advances wound repair. Also, the GJIC between mast cells and fibroblasts during the remodeling phase of repair may explain how mast cells promote excessive scarring. In addition, Cx can affect transforming growth factor beta (TGF-β) intracellular signaling through its shared binding site on microtubules within fibroblasts. Can excessive scarring be controlled through limiting the local amassing of mast cells or preventing their interactions with wound fibroblasts through GJIC? The prevention of the accumulation of mast cells in granulation tissue or interfering with their communications via GJIC with fibroblasts offers new approaches for preventing excess scarring. The association of Cx with microtubules altering TGF-β signaling presents a new target for improving the quality of repair as well as the deposition of unnecessary fibrosis.
    No preview · Article · May 2013
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate whether administrating Abnormal Savda Munziq (ASMq), a traditional Uighur herbal preparation used for the prevention or treatment of diseases, affects hypertrophic scar (HTS) formation by using an established rabbit ear model. The HTS rabbit model was created by circular fullthickness skin excisions on both ears of rabbits. Twenty rabbits were randomized into four groups, with 5 rabbits and 60 wounds in each group. Group A was the control group, treated with normal saline daily. Groups B, C, and D were the treatment groups at three different doses of ASMq (400, 800, and 1200 mg/kg body weight, respectively, daily, by gastrogavage). Twenty wounds were randomly chosen from each group on the 40th day after treatment and specimen were examined. Scar elevation index (SEI) was analyzed with histological assessment, and ultrastructure analysis was analyzed with a transmission electron microscopy. Groups B, C, and D demonstrated significant reductions in SEI as compared with the control group at 35.9% (P =0.0212), 48.2% (P =0.0108), and 52.7% (P =0.0103), respectively in a dose-response manner. SEI was lowered in Group D compared with Group B with a significant difference (P =0.015). However, there were no significant differences between Groups B and C, or between Groups C and D. Histological analysis showed that highdose ASMq (1200 mg/kg) could enhance the softening of HTS of rabbit ears and increase the compliance as shown in general. Ultrastructure analysis showed that with increased ASMq dose, the fibroblasts, pro-collagen, collagen, endoplasmic reticulum and ribosomes were reduced gradually. Orally administered ASMq significantly reduces the severity of HTS in the rabbit ear model. The findings of this study may have clinical implications on the management of human HTS.
    No preview · Article · Jan 2014 · Chinese Journal of Integrative Medicine
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Most cutaneous wounds heal with scar formation. Ideally, an inconspicuous normotrophic scar is formed, but an abnormal scar (hypertrophic scar or keloid) can also develop. A major challenge to scientists and physicians is to prevent adverse scar formation after severe trauma (e.g. burn injury) and understand why some individuals will form adverse scars even after relatively minor injury. Currently many different models exist to study scar formation, ranging from simple monolayer cell culture to 3D tissue engineered models even to humanized mouse models. Currently these high/ medium throughput test models avoid the main questions referring to why an adverse scar forms instead of a normotrophic scar and what causes a hypertrophic scar to form rather than a keloid scar. Also, how is the genetic pre-disposition of the individual and the immune system involved. This information is essential if we are to identify new drug targets and develop optimal strategies in the future to prevent adverse scar formation. This viewpoint review summarizes the progress on in vitro and animal scar models, stresses the limitations in the current models and identifies the future challenges if scar free healing is to be achieved in the future. This article is protected by copyright. All rights reserved.
    Full-text · Article · Apr 2014 · Experimental Dermatology
Show more