The FASEB Journal, Vol 6, 2397-2404, Copyright © 1992 by The Federation of American Societies for Experimental Biology

REVIEWS

Hyaluronan

TC Laurent and JR Fraser
Department of Medical and Physiological Chemistry, University of Uppsala, Sweden.

Hyaluronan (hyaluronic acid) is a high-molecular-mass polysaccharide found in the extracellular matrix, especially of soft connective tissues. It is synthesized in the plasma membrane of fibroblasts and other cells by addition of sugars to the reducing end of the polymer, whereas the nonreducing end protrudes into the pericellular space. The polysaccharide is catabolized locally or carried by lymph to lymph nodes or the general circulation, from where it is cleared by the endothelial cells of the liver sinusoids. The overall turnover rate is surprisingly rapid for a connective tissue matrix component (t1/2 0.5 to a few days). Hyaluronan has been assigned various physiological functions in the intercellular matrix, e.g., in water and plasma protein homeostasis. Hyaluronan production increases in proliferating cells and the polymer may play a role in mitosis. Extensive hyaluronidase-sensitive coats have been identified around mesenchymal cells. They are either anchored firmly in the plasma membrane or bound via hyaluronan-specific binding proteins (receptors). Such receptors have now been identified on many different cells, e.g., the lymphocyte homing receptor CD 44. Interaction between a hyaluronan receptor and extracellular polysaccharide has been connected with locomotion and cell migration. Hyaluronan seems to play an important role during development and differentiation and has other cell regulatory activities. Hyaluronan has also been recognized in clinical medicine. A concentrated solution of hyaluronan (10 mg/ml) has, through its tissue protective and rheological properties, become a device in ophthalmic surgery. Analysis of serum hyaluronan is promising in the diagnosis of liver disease and various inflammatory conditions, e.g., rheumatoid arthritis. Interstitial edema caused by accumulation of hyaluronan may cause dysfunction in various organs.

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				T Pham, A Le Henanff, P. Ravaud, P Dieppe, L Paolozzi, and M Dougados Evaluation of the symptomatic and structural efficacy of a new hyaluronic acid compound, NRD101, in comparison with diacerein and placebo in a 1 year randomised controlled study in symptomatic knee osteoarthritis Ann Rheum Dis, December 1, 2004; 63(12): 1611 - 1617. [Abstract] [Full Text] [PDF]

				A. Botzki, D. J. Rigden, S. Braun, M. Nukui, S. Salmen, J. Hoechstetter, G. Bernhardt, S. Dove, M. J. Jedrzejas, and A. Buschauer L-Ascorbic Acid 6-Hexadecanoate, a Potent Hyaluronidase Inhibitor: X-RAY STRUCTURE AND MOLECULAR MODELING OF ENZYME-INHIBITOR COMPLEXES J. Biol. Chem., October 29, 2004; 279(44): 45990 - 45997. [Abstract] [Full Text] [PDF]

				W. Jing and P. L. DeAngelis Synchronized Chemoenzymatic Synthesis of Monodisperse Hyaluronan Polymers J. Biol. Chem., October 1, 2004; 279(40): 42345 - 42349. [Abstract] [Full Text] [PDF]

				E. N. Harris, J. A. Weigel, and P. H. Weigel Endocytic Function, Glycosaminoglycan Specificity, and Antibody Sensitivity of the Recombinant Human 190-kDa Hyaluronan Receptor for Endocytosis (HARE) J. Biol. Chem., August 27, 2004; 279(35): 36201 - 36209. [Abstract] [Full Text] [PDF]

				I. Kakizaki, K. Kojima, K. Takagaki, M. Endo, R. Kannagi, M. Ito, Y. Maruo, H. Sato, T. Yasuda, S. Mita, et al. A Novel Mechanism for the Inhibition of Hyaluronan Biosynthesis by 4-Methylumbelliferone J. Biol. Chem., August 6, 2004; 279(32): 33281 - 33289. [Abstract] [Full Text] [PDF]

				T. Itoh, S. Akao, W. Hashimoto, B. Mikami, and K. Murata Crystal Structure of Unsaturated Glucuronyl Hydrolase, Responsible for the Degradation of Glycosaminoglycan, from Bacillus sp. GL1 at 1.8 A Resolution J. Biol. Chem., July 23, 2004; 279(30): 31804 - 31812. [Abstract] [Full Text] [PDF]

				S. J. King, A. G. Allen, D. J. Maskell, C. G. Dowson, and A. M. Whatmore Distribution, Genetic Diversity, and Variable Expression of the Gene Encoding Hyaluronate Lyase within the Streptococcus suis Population J. Bacteriol., July 15, 2004; 186(14): 4740 - 4747. [Abstract] [Full Text] [PDF]

				M. Ohno-Nakahara, K. Honda, K. Tanimoto, N. Tanaka, T. Doi, A. Suzuki, K. Yoneno, Y. Nakatani, M. Ueki, S. Ohno, et al. Induction of CD44 and MMP Expression by Hyaluronidase Treatment of Articular Chondrocytes J. Biochem., May 1, 2004; 135(5): 567 - 575. [Abstract] [Full Text] [PDF]

				W. Selbi, C. de la Motte, V. Hascall, and A. Phillips BMP-7 Modulates Hyaluronan-Mediated Proximal Tubular Cell-Monocyte Interaction J. Am. Soc. Nephrol., May 1, 2004; 15(5): 1199 - 1211. [Abstract] [Full Text] [PDF]

				N. Itano, T. Sawai, F. Atsumi, O. Miyaishi, S. Taniguchi, R. Kannagi, M. Hamaguchi, and K. Kimata Selective Expression and Functional Characteristics of Three Mammalian Hyaluronan Synthases in Oncogenic Malignant Transformation J. Biol. Chem., April 30, 2004; 279(18): 18679 - 18687. [Abstract] [Full Text] [PDF]

				K. R. Taylor, J. M. Trowbridge, J. A. Rudisill, C. C. Termeer, J. C. Simon, and R. L. Gallo Hyaluronan Fragments Stimulate Endothelial Recognition of Injury through TLR4 J. Biol. Chem., April 23, 2004; 279(17): 17079 - 17084. [Abstract] [Full Text] [PDF]

				V. Goransson, C. Johnsson, A. Jacobson, P. Heldin, R. Hallgren, and P. Hansell Renal hyaluronan accumulation and hyaluronan synthase expression after ischaemia-reperfusion injury in the rat Nephrol. Dial. Transplant., April 1, 2004; 19(4): 823 - 830. [Abstract] [Full Text] [PDF]

				S. J. LAI-FOOK Pleural Mechanics and Fluid Exchange Physiol Rev, April 1, 2004; 84(2): 385 - 410. [Abstract] [Full Text] [PDF]

				C.-T. Wang, J. Lin, C.-J. Chang, Y.-T. Lin, and S.-M. Hou Therapeutic Effects of Hyaluronic Acid on Osteoarthritis of the Knee. A Meta-Analysis of Randomized Controlled Trials J. Bone Joint Surg. Am., March 1, 2004; 86(3): 538 - 545. [Abstract] [Full Text] [PDF]

				K. M. Stuhlmeier and C. Pollaschek Glucocorticoids inhibit induced and non-induced mRNA accumulation of genes encoding hyaluronan synthases (HAS): hydrocortisone inhibits HAS1 activation by blocking the p38 mitogen-activated protein kinase signalling pathway Rheumatology, February 1, 2004; 43(2): 164 - 169. [Abstract] [Full Text] [PDF]

				K. Tanimoto, A. Suzuki, S. Ohno, K. Honda, N. Tanaka, T. Doi, K. Yoneno, M. Ohno-Nakahara, Y. Nakatani, M. Ueki, et al. Effects of TGF-{beta} on Hyaluronan Anabolism in Fibroblasts Derived from the Synovial Membrane of the Rabbit Temporomandibular Joint Journal of Dental Research, January 1, 2004; 83(1): 40 - 44. [Abstract] [Full Text] [PDF]

				S. Esnault and J. S. Malter Hyaluronic Acid or TNF-{alpha} Plus Fibronectin Triggers Granulocyte Macrophage-Colony-Stimulating Factor mRNA Stabilization in Eosinophils Yet Engages Differential Intracellular Pathways and mRNA Binding Proteins J. Immunol., December 15, 2003; 171(12): 6780 - 6787. [Abstract] [Full Text] [PDF]

				D. J. Rigden and M. J. Jedrzejas Structures of Streptococcus pneumoniae Hyaluronate Lyase in Complex with Chondroitin and Chondroitin Sulfate Disaccharides: INSIGHTS INTO SPECIFICITY AND MECHANISM OF ACTION J. Biol. Chem., December 12, 2003; 278(50): 50596 - 50606. [Abstract] [Full Text] [PDF]

				M. Ikegami-Kawai, A. Suzuki, I. Karita, and T. Takahashi Increased Hyaluronidase Activity in the Kidney of Streptozotocin-Induced Diabetic Rats J. Biochem., December 1, 2003; 134(6): 875 - 880. [Abstract] [Full Text] [PDF]

				H Xu, J Edwards, S Banerji, R Prevo, D G Jackson, and N A Athanasou Distribution of lymphatic vessels in normal and arthritic human synovial tissues Ann Rheum Dis, December 1, 2003; 62(12): 1227 - 1229. [Abstract] [Full Text] [PDF]

				J. A. Weigel and P. H. Weigel Characterization of the Recombinant Rat 175-kDa Hyaluronan Receptor for Endocytosis (HARE) J. Biol. Chem., October 31, 2003; 278(44): 42802 - 42811. [Abstract] [Full Text] [PDF]

				M. Takeda, H. Terasawa, M. Sakakura, Y. Yamaguchi, M. Kajiwara, H. Kawashima, M. Miyasaka, and I. Shimada Hyaluronan Recognition Mode of CD44 Revealed by Cross-saturation and Chemical Shift Perturbation Experiments J. Biol. Chem., October 31, 2003; 278(44): 43550 - 43555. [Abstract] [Full Text] [PDF]

				S. Desrivieres, T. Prinz, N. Castro-Palomino Laria, M. Meyer, G. Boehm, U. Bauer, J. Schafer, T. Neumann, C. Shemanko, and B. Groner Comparative Proteomic Analysis of Proliferating and Functionally Differentiated Mammary Epithelial Cells Mol. Cell. Proteomics, October 1, 2003; 2(10): 1039 - 1054. [Abstract] [Full Text] [PDF]

				G. Acunzo, M. Guida, M. Pellicano, G. A. Tommaselli, A. Di Spiezio Sardo, G. Bifulco, D. Cirillo, A. Taylor, and C. Nappi Effectiveness of auto-cross-linked hyaluronic acid gel in the prevention of intrauterine adhesions after hysteroscopic adhesiolysis: a prospective, randomized, controlled study Hum. Reprod., September 1, 2003; 18(9): 1918 - 1921. [Abstract] [Full Text] [PDF]

				W. Yingsung, L. Zhuo, M. Morgelin, M. Yoneda, D. Kida, H. Watanabe, N. Ishiguro, H. Iwata, and K. Kimata Molecular Heterogeneity of the SHAP-Hyaluronan Complex: ISOLATION AND CHARACTERIZATION OF THE COMPLEX IN SYNOVIAL FLUID FROM PATIENTS WITH RHEUMATOID ARTHRITIS J. Biol. Chem., August 29, 2003; 278(35): 32710 - 32718. [Abstract] [Full Text] [PDF]

				K. N. Sugahara, T. Murai, H. Nishinakamura, H. Kawashima, H. Saya, and M. Miyasaka Hyaluronan Oligosaccharides Induce CD44 Cleavage and Promote Cell Migration in CD44-expressing Tumor Cells J. Biol. Chem., August 22, 2003; 278(34): 32259 - 32265. [Abstract] [Full Text] [PDF]