Keratan sulfate

About: Keratan sulfate is a research topic. Over the lifetime, 1253 publications have been published within this topic receiving 57984 citations. The topic is also known as: keratan sulfate & KS.

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

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.

Lumican expression is positively correlated with the differentiation and negatively with the growth of human osteosarcoma cells

Abstract: Osteosarcoma is the most common primary bone tumour associated with childhood and adolescence. The possible role of the small leucine-rich proteoglycan, lumican, in the growth and metastasis of various cancer types has recently been investigated. In this study, the expression of lumican was examined in moderately differentiated (MG-63) and well-differentiated (Saos 2) human osteosarcoma cell lines of high and low metastatic capability, respectively. Real-time PCR, western blotting with antibodies against the protein core and keratan sulfate, and specific enzymatic digestions were the methods employed. The two human osteosarcoma cell lines were found to express and secrete lumican partly substituted with keratan sulfate glycosaminoglycans. Importantly, the non-metastatic, well-differentiated Saos 2 cells produced lumican at rates that were up to sevenfold higher than those of highly metastatic MG-63 cells. The utilization of short interfering RNA specific for the lumican gene resulted in efficient down-regulation of its mRNA levels in both cell lines. The growth of Saos 2 cells was inhibited by lumican, whereas their migration and chemotactic response to fibronectin were found to be promoted. Lumican expression was negatively correlated with the basal level of Smad 2 activation in these cells, suggesting that lumican may affect the bioavailability of Smad 2 activators. By contrast, these cellular functions of highly aggressive MG-63 cells were demonstrated not to be sensitive to a decrease in their low endogenous lumican levels. These results suggest that lumican expression may be positively correlated with the differentiation and negatively correlated with the progression of osteosarcoma.

Matrix morphogenesis in cornea is mediated by the modification of keratan sulfate by GlcNAc 6-O-sulfotransferase.

Abstract: Matrix assembly and homeostasis in collagen-rich tissues are mediated by interactions with proteoglycans (PGs) substituted with sulfated glycosaminoglycans (GAGs). The major GAG in cornea is keratan sulfate (KS), which is N-linked to one of three PG core proteins. To ascertain the importance of the carbohydrate chain sulfation step in KS functionality, we generated a strain of mice with a targeted gene deletion in Chst5, which encodes an N-acetylglucosamine-6-O-sulfotransferase that is integral to the sulfation of KS chains. Corneas of homozygous mutants were significantly thinner than those of WT or heterozygous mice. They lacked high-sulfated KS, but contained the core protein of the major corneal KSPG, lumican. Histochemically stained KSPGs coassociated with fibrillar collagen in WT corneas, but were not identified in the Chst5-null tissue. Conversely, abnormally large chondroitin sulfate/dermatan sulfate PG complexes were abundant throughout the Chst5-deficient cornea, indicating an alteration of controlled PG production in the mutant cornea. The corneal stroma of the Chst5-null mouse exhibited widespread structural alterations in collagen fibrillar architecture, including decreased interfibrillar spacing and a more spatially disorganized collagen array. The enzymatic sulfation of KS GAG chains is thus identified as a key requirement for PG biosynthesis and collagen matrix organization.