Respective roles of hyaluronidases 1 and 2 in endogenous hyaluronan turnover

Abstract

We studied the physiologic roles of the hyaluronidase (HYAL) 1 and HYAL2 in hyaluronan (HA) turnover. HA was localized and quantified using HA binding proteins in various tissues of Hyal1 2/2 and Hyal2 2/2 mice (knockout mice) as well as control mice. HA MW was determined using gel filtration chromatography. HA endocytosis in liver nonparenchymal cells (NPCs) was quantified in vivo. Both Hyal1 and Hyal2 knockout mice showed HA accumulation in peripheral tissues without changes in HA MW distribution. HYAL2 deficiency induced buildup of very high MW (>3.10 6 Da) HA in lymph and serum with severe lymph node distortion. The lack of HYAL2 also impaired high MW HA endocytosis by liver NPCs. HYAL1 deficiency led to a moderate increase in serum HA concentration without changes in HA MW distribution and to HA overload of liver NPCs. Wild-type C57BL/6 mice served as controls. In HA injection experiments, saline-injected mice served as additional controls. We conclude that: 1) HYAL1 and HYAL2 are both needed for tissue HA catabolism; 2) HYAL2 is required for high MW HA clearance in lymph nodes and plasma and for HA endocytosis by liver NPCs; and 3) the main role of HYAL1 is HA degradation within liver NPCs.-Bourguignon, V., Flamion, B. Respective roles of hyaluronidases 1 and 2 in endogenous hyaluronan turnover. FASEB J. 30, 2108FASEB J. 30, -2114FASEB J. 30, (2016. www.fasebj.org

Hyaluronidase 1 Deficiency Preserves Endothelial Function and Glycocalyx Integrity in Early Streptozotocin-Induced Diabetes

“…However, the difference in plasma HA concentrations between diabetic WT mice and diabetic HYAL1 KO mice in our study was only moderate (+58% in the latter) and unlikely to explain the large difference in glycocalyx HA content during exposure of WT versus KO mice to hyperglycemia. Additionally, we have shown similar molecular size profiles of circulating HA in HYAL1 KO and WT mice (44). Finally, the hypothesis that higher baseline expression of SK3 would explain a thicker glycocalyx seems unlikely based on the known function of SK3.…”

Extracellular matrix alterations in the Peyronie’s disease

“…Nevertheless, low molecular weight HA seems to be involved in the inflammation process, inducing the production of cytokines and contributing to macrophage activation as well as angiogenesis [20], [21], [22]. Furthermore, high molecular weight HA was synthesized by HAS1 and HAS2, while HAS3 is involved in the synthesis of low molecular weight HA, and HA was degraded essentially by Hyl1 and Hyal2 [23], [24]. No alterations observed in the expression of the enzymes involved in the synthesis and degradation of HA validate the result, which showed no difference in the quantification of this glycosaminoglycan in both Peyronie’s and control tissues.…”

HYAL-2–WWOX–SMAD4 Signaling in Cell Death and Anticancer Response

“…No HYAL2 deficiency has been found in human. Hyal2 -deficient mice exhibit accumulation of extremely large HA molecules in tissues and in circulation, and this contributes to the development of chronic thrombotic microangiopathy (Onclinx et al, 2015) and mild craniofacial and vertebral abnormalities (Bourguignon and Flamion, 2016). Megakaryocyte-derived HYAL-2 causes HA degradation, which is needed for thrombopoiesis (Petrey et al, 2016).…”