Abstract
Background/Purpose
Mid-gestational (E14.5) fetal wounds heal regeneratively with attenuated inflammation
and high levels of hyaluronan (HA) in their extracellular matrix (ECM), whereas late-gestational
(E18.5) fetal wounds heal with scarring. IL-10 plays an essential role in the fetal
regenerative phenotype and is shown to recapitulate scarless wound healing postnatally.
We hypothesize a novel role of IL-10 as a regulator of HA in the ECM.
Methods
Murine fetal fibroblasts (FFb) from C57Bl/6 and IL-10−/− mice were evaluated in vitro. Pericellular matrix (PCM) and HA synthesis were
quantified using a particle exclusion assay and ELISA. The effects of hyaluronidase
and hyaluronan synthase (HAS) inhibitor (4-methylumbelliferone[4-MU]) were evaluated.
An ex vivo fetal forearm culture incisional wound model comparing mid-gestation and
late-gestation fetuses was used to evaluate IL-10's effect on HA-rich ECM production
with pentachrome and immunohistochemistry.
Results
FFb produce a robust HA-rich PCM which is IL-10 dependent and attenuated with hyaluronidase
and HAS inhibition. Mid-gestation fetal wounds produce more ground substance and HA
than late-gestation fetal wounds. IL-10 in late-gestation fetal wounds results in
elevated ground substance levels and HA staining.
Conclusions
Our data demonstrate that IL-10 regulates an HA-rich ECM deposition, suggesting a
novel non-immunoregulatory mechanism of IL-10 in mediating regenerative wound healing.
Key words
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Article info
Publication history
Accepted:
March 8,
2013
Received:
February 22,
2013
Identification
Copyright
© 2013 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
