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PLoS One. 2015 May 7;10(5):e0124302. doi: 10.1371/journal.pone.0124302. eCollection 2015.

The role of interleukin-10 and hyaluronan in murine fetal fibroblast function in vitro: implications for recapitulating fetal regenerative wound healing.

Author information

1
Laboratory for Regenerative Wound Healing, Division of Pediatric, General, Thoracic and Fetal Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
2
Division of Infectious Diseases, Department of Medicine, Stanford University School of Medicine, Palo Alto, California, United States of America.
3
Laboratory for Regenerative Wound Healing, Division of Pediatric, General, Thoracic and Fetal Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America; Center for Children's Surgery, Children's Hospital Colorado and The University of Colorado School of Medicine, Aurora, Colorado, United States of America.
4
Laboratory for Regenerative Wound Healing, Division of Pediatric, General, Thoracic and Fetal Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America; Division of Pediatric General and Thoracic Surgery, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, United States of America.

Abstract

BACKGROUND:

Mid-gestation fetal cutaneous wounds heal scarlessly and this has been attributed in part to abundant hyaluronan (HA) in the extracellular matrix (ECM) and a unique fibroblast phenotype. We recently reported a novel role for interleukin 10 (IL-10) as a regulator of HA synthesis in the fetal ECM, as well as the ability of the fetal fibroblast to produce an HA-rich pericellular matrix (PCM). We hypothesized that IL-10-mediated HA synthesis was essential to the fetal fibroblast functional phenotype and, moreover, that this phenotype could be recapitulated in adult fibroblasts via supplementation with IL-10 via an HA dependent process.

METHODOLOGY/PRINCIPAL FINDINGS:

To evaluate the differences in functional profile, we compared metabolism (MTS assay), apoptosis (caspase-3 staining), migration (scratch wound assay) and invasion (transwell assay) between C57Bl/6J murine fetal (E14.5) and adult (8 weeks) fibroblasts. We found that fetal fibroblasts have lower rates of metabolism and apoptosis, and an increased ability to migrate and invade compared to adult fibroblasts, and that these effects were dependent on IL-10 and HA synthase activity. Further, addition of IL-10 to adult fibroblasts resulted in increased fibroblast migration and invasion and recapitulated the fetal phenotype in an HA-dependent manner.

CONCLUSIONS/SIGNIFICANCE:

Our data demonstrates the functional differences between fetal and adult fibroblasts, and that IL-10 mediated HA synthesis is essential for the fetal fibroblasts' enhanced invasion and migration properties. Moreover, IL-10 via an HA-dependent mechanism can recapitulate this aspect of the fetal phenotype in adult fibroblasts, suggesting a novel mechanism of IL-10 in regenerative wound healing.

PMID:
25951109
PMCID:
PMC4423847
DOI:
10.1371/journal.pone.0124302
[Indexed for MEDLINE]
Free PMC Article

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