Interleukin-10 regulates fetal extracellular matrix hyaluronan production

J Pediatr Surg. 2013 Jun;48(6):1211-1217. doi: 10.1016/j.jpedsurg.2013.03.014.


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.

Keywords: Extracellular matrix; Fetal; Hyaluronan; IL-10; Wound healing.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Matrix / metabolism*
  • Fetal Development / physiology*
  • Hyaluronic Acid / metabolism*
  • Immunohistochemistry
  • Interleukin-10 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Organ Culture Techniques
  • Wound Healing / physiology*


  • Biomarkers
  • IL10 protein, mouse
  • Interleukin-10
  • Hyaluronic Acid