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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- Studies in fetal wound healing, VI. Second and early third trimester fetal wounds demonstrate rapid collagen deposition without scar formation.J Pediatr Surg. 1990; 25 ([discussion 68-69]): 63-68
- Fetal response to injury in the rabbit.J Pediatr Surg. 1987; 22: 640-644
- Effect of fetal serum on fibroblast pericellular matrix formation.J Surg Res. 1996; 64: 128-131
- Fetal wound healing: implications for minimal scar formation.Curr Opin Pediatr. 2012; 24: 371-378
- Comparison of fetal, newborn, and adult wound healing by histologic, enzyme-histochemical, and hydroxyproline determinations.J Pediatr Surg. 1985; 20: 315-319
- Permissive environment in postnatal wounds induced by adenoviral-mediated overexpression of the anti-inflammatory cytokine interleukin-10 prevents scar formation.Wound Repair Regen. 2008; 16: 70-79
- Fetal wound repair results in scar formation in interleukin-10-deficient mice in a syngeneic murine model of scarless fetal wound repair.J Pediatr Surg. 2000; 35 ([discussion 872–863]): 866-872
- IL-10 overexpression decreases inflammatory mediators and promotes regenerative healing in an adult model of scar formation.J Invest Dermatol. 2008; 128: 1852-1860
- Generation of hyaline cartilaginous tissue from mouse adult dermal fibroblast culture by defined factors.J Clin Invest. 2011; 121: 640-657
- Hyaluronan induces scarless repair in mouse limb organ culture.J Pediatr Surg. 1998; 33: 564-567
- Interleukin-10 and the interleukin-10 receptor.Annu Rev Immunol. 2001; 19: 683-765
- Macrophage deactivation by interleukin 10.J Exp Med. 1991; 174: 1549-1555
- Interleukin-10 messenger ribonucleic acid in human placenta: implications of a role for interleukin-10 in fetal allograft protection.Am J Obstet Gynecol. 1995; 173: 25-29
- Interleukin-10 in amniotic fluid at midtrimester: immune activation and suppression in relation to fetal growth.Am J Obstet Gynecol. 1994; 171: 55-59
- Hyaluronate metabolism undergoes an ontogenic transition during fetal development: implications for scar-free wound healing.J Pediatr Surg. 1993; 28: 1227-1231
- Biology of fetal wound healing: hyaluronate receptor expression in fetal fibroblasts.J Pediatr Surg. 1994; 29: 1040-1043
- The role of hyaluronan produced by Has2 gene expression in development of the spine.Spine (Phila Pa 1976). 2011; 36: E914-E920
Accepted: March 8, 2013
Received: February 22, 2013
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