Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.36 (hyaluronidase)
 4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cumulus cells surround the oocyte and regulate the production and assembly of the extracellular matrix (ECM) around the cumulus-oocyte complex for its timely interaction with sperm in the oviduct. We recently found that C-C chemokines such as CCL2, CCL7, and CCL9 are produced and stimulate integrin-mediated ECM assembly in the postovulatory cumulus to protect eggs and that prostaglandin E(2)-EP2 signaling in the cumulus cells facilitates fertilization by suppressing this chemokine signaling, which otherwise results in fertilization failure by preventing sperm penetration through the cumulus ECM. However, it remains unknown as to what mechanisms underlie chemokine-induced cumulus ECM assembly. Here we report that inhibition of EP2 signaling or addition of CCL7 augments RhoA activation and induces the surface accumulation of integrin and the contraction of cumulus cells. Enhanced surface accumulation of integrin then stimulates the formation and assembly of fibronectin fibrils as well as induces cumulus ECM resistance to hyaluronidase and sperm penetration. These changes in the cumulus ECM as well as cell contraction are relieved by the addition of Y27632 or blebbistatin. These results suggest that chemokines induce integrin engagement to the ECM and consequent ECM remodeling through the RhoA/Rho kinase/actomyosin pathway, making the cumulus ECM barrier resistant to sperm penetration. Based on these results, we propose that prostaglandin E(2)-EP2 signaling negatively regulates chemokine-induced Rho/ROCK signaling in cumulus cells for successful fertilization.
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PMID:RhoA/Rho kinase signaling in the cumulus mediates extracellular matrix assembly. 1934 61

Aberrant hyaluronan production has been implicated in many types of tumor. In this context, hyaluronidase has been explored as a viable therapeutic approach to reduce tumoral hyaluronan. However, elevated levels of hyaluronan in tumors are often associated with high expression levels of cellular hyaluronidases, which consequently produce various sizes of saturated hyaluronan fragments with divergent pro-tumoral activities. The current study shows that different hyaluronan metabolisms of mammalian and microbial hyaluronidases could elicit distinct alterations in cancer cell behavior. Unlike saturated hyaluronan metabolites, unsaturated hyaluronan oligosaccharides produced by bacteriophage hyaluronidase, HylP, had no biological effect on growth of breast carcinoma cells. More importantly, HylP's metabolic process of hyaluronan into non-detrimental oligosaccharides significantly decreased breast cancer cell proliferation, migration and invasion by disrupting Erk1/2 activation and RhoA expression. Our results suggest that it may be possible to exploit HylP's unique enzymatic activity in suppressing hyaluronan-mediated tumor growth and progression.
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PMID:Bacteriophage hyaluronidase effectively inhibits growth, migration and invasion by disrupting hyaluronan-mediated Erk1/2 activation and RhoA expression in human breast carcinoma cells. 2068 28

The design of hyaluronic acid (HA)-based and stimuli-responsive hydrogels to elicit highly controlled and tunable cell response and behaviors is a major field of interest in tissue engineering and regenerative medicine. The pH-responsive hydrogel can respond to pH variation during wound healing, which may in turn regulate the tissue regeneration process. In this study, a double-network hydrogel cross-linked with vinyl double bonds and Schiff base was prepared, whose properties were further adjusted by incubation in pH 7.4 and pH 5 buffers. The endothelial cells (ECs) migrated much deeper into the softer HA hydrogel pre-treated with pH 5 buffer than the stiffer hydrogel. By contrast, the mesenchymal stem cells (MSCs) migrated easily into the stiffer hydrogel. The ECs highly expressed RhoA and non-muscle myosin (NM) II genes in the softer hydrogel, which may facilitate amoeboid migration. Meanwhile, the MSCs were stiffer than the ECs, and highly expressed Rac1, RhoA, vinculin, NM II, hyaluronidase (HYAL) 2 and CD44 genes in the stiffer hydrogel, which facilitate mesenchymal migration. These results provide important clues for revealing the different migration strategies of the ECs and MSCs in HA hydrogels with different stiffness, and suggest that the mechanical properties and the network structure of hydrogels play an important role in regulating the three-dimensional migration process of these cells.
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PMID:Migration of endothelial cells and mesenchymal stem cells into hyaluronic acid hydrogels with different moduli under induction of pro-inflammatory macrophages. 3141 53