Soluble lumican glycoprotein purified from human amniotic membrane promotes corneal epithelial wound healing.

TLDR: The diversified functions of lumican include modulation of epithelial cells in wound healing and serving as an extracellular matrix component in human amniotic membrane.

Abstract: Lumican, a small leucine-rich proteoglycan (SLRP), is one of the major extracellular components in interstitial collagenous matrices of the corneal stroma, aorta, skin, skeletal muscle, lung, kidney, bone, cartilage, and intervertebral discs.1–8 In the cornea, lumican contains keratan sulfate chains. However, it is present as a low or nonsulfated glycoprotein (50 –57 kDa) in noncorneal tissues.1,2,9–11 Its wide distribution implies that it has multiple functions in tissue morphogenesis and maintenance of tissue homeostasis. This is best illustrated by the multiple clinical manifestations observed in Lumican-knockout (lum−/−) mice that exhibit corneal opacity, skin and tendon fragility, delayed wound healing, and low fertility. Indeed, lumican has been shown to play essential roles in corneal transparency by regulating collagen fibrillogenesis8 in wound healing, by modulating epithelial cell migration,12 and in the epithelium–mesenchyme transition of the injured lens.13 These results have led to the speculation that lumican may play an active role in corneal epithelial wound healing. Transplantation of human AM as a temporary or permanent graft has become a popular surgical procedure for ocular surface reconstruction.14,15 Besides the observation that cryopreserved AM reduces inflammation,16–21 scarring,22,23 and neovascularization,24 many clinical studies25–28 have shown that human AM as a graft promotes corneal epithelial wound healing. Furthermore, human AM can help preserve corneal limbal epithelial progenitor cells and maintain the keratocyte phenotype during ex vivo expansion.29–32 Nevertheless, the exact molecular mechanism of the aforementioned effects remains unknown. The present study revealed that human AM is a rich source of soluble lumican glycoprotein and that purified soluble lumican glycoprotein can facilitate proliferation and migration of corneal epithelial cells during wound healing in both wild-type and lum−/− mice.