Interleukin-10 regulates fetal extracellular matrix hyaluronan production.

Interleukin-10 regulates fetal extracellular matrix hyaluronan production.
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DOI:
10.1016/j.jpedsurg.2013.03.014
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发表时间:
2013-06
影响因子:
2.4
通讯作者:
Keswani, Sundeep G.
Keswani, Sundeep G.
中科院分区:
医学3区
文献类型:
--
作者:
King, Alice;Balaji, Swathi;Le, Louis D.;Marsh, Emily;Crombleholme, Timothy M.;Keswani, Sundeep G.

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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. 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. 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. 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.
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