Hyaluronidase 1 and hyaluronidase 2 are required for renal hyaluronan turnover

Colombaro, Vanessa; Jadot, Inès; Declèves, Anne Émilie; Voisin, Virginie; Giordano, Laetitia; Habsch, Isabelle; Flamion, Bruno; Caron, Nathalie

doi:10.1016/j.acthis.2014.11.007

Cited by 12 publications

(8 citation statements)

References 31 publications

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“…We conclude that HYAL2 is at least as important as HYAL1 in peripheral tissue HA turnover. A similar conclusion was previously reached for the kidney (30).…”

Section: Discussionsupporting

confidence: 89%

Respective roles of hyaluronidases 1 and 2 in endogenous hyaluronan turnover

Bourguignon

Flamion

2016

FASEB j.

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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

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“…We conclude that HYAL2 is at least as important as HYAL1 in peripheral tissue HA turnover. A similar conclusion was previously reached for the kidney (30).…”

Section: Discussionsupporting

confidence: 89%

Respective roles of hyaluronidases 1 and 2 in endogenous hyaluronan turnover

Bourguignon

Flamion

2016

FASEB j.

Self Cite

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“…However, no studies have been performed to describe how HYAL2 contributes to kidney development/pathology. Several in vitro and expression studies have been reported that HA and HYALs might play a significant contribution to kidney development and disease [237,238]. During the development of the chick embryonic kidney (day [11][12][13][14][15][16][17][18], reduced levels of HA and increased HYALs were demonstrated [237].…”

Section: Discussionmentioning

confidence: 99%

Hyaluronidase 2 (HYAL2) is expressed in endothelial cells, as well as some specialized epithelial cells, and is required for normal hyaluronan catabolism

Chowdhury

Hemming

Faiyaz

et al. 2015

Histochem Cell Biol

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Hyaluronidase 2 (HYAL2) is a membrane-anchored protein that is proposed to initiate the degradation of hyaluronan (HA) in the extracellular matrix. The distribution of HYAL2 in tissues, and of HA in tissues lacking HYAL2, is largely unexplored despite the importance of HA metabolism in several disease processes. Herein, we use immunoblot and histochemical analyses to detect HYAL2 and HA in mouse tissues, as well as agarose gel electrophoresis to examine the size of HA. HYAL2 was detected in all tissues that were examined, including the brain. It was localized to the surface and cytoplasm of endothelial cells, as well as specialized epithelial cells in several tissues, including the skin. Accumulated HA, often of higher molecular mass than that in control tissues, was detected in tissues from Hyal2 (-/-) mice. The accumulating HA was located near to where HYAL2 is normally found, although in some tissues, it was distant from the site of HYAL2 localization. Overall, HYAL2 was highest in tissues that remove HA from the circulation (liver, lymph node and spleen), but the levels of HA accumulation in Hyal2 (-/-) mice were highest in tissues that catabolize locally synthesized HA. Our results support HYAL2's role as an extracellular enzyme that initiates HA breakdown in somatic tissues. However, our findings also suggest that HYAL2 contributes to HA degradation through other routes, perhaps as a soluble or secreted form.

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“…Catabolic HA enzymes, specifically HYALs 1 and 2, cleave HMW-HA into LMW-HA and oligosaccharides [ 14 , 15 ], with deficiency of these two HYALs leading to malfunction of organs like the kidney [ 16 ], heart [ 17 ], and lungs [ 18 ]. Conversely, HA accumulation has not been observed in Hyal3 knockout mice [ 15 ], suggesting that Hyals 1 and 2 may compensate for the loss of Hyal3 .…”

Section: Hyaluronic Acid and Its Biological And Physiological Propertiesmentioning

confidence: 99%

Hyaluronan, a double-edged sword in kidney diseases

et al. 2021

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Over the years, hyaluronic acid (HA) has emerged as an important molecule in nephrological and urological studies involving extracellular matrix (ECM) organization, inflammation, tissue regeneration, and viral sensing. During this time, many have noted the perplexing double-edged nature of the molecule, at times promoting pro-fibrotic events and at other times promoting anti-fibrotic events. Different molecular weights of HA can be attributed to these disparities, though most studies have yet to focus on this subtlety. With regard to the kidney, HA is induced in the initial response phase of injury and is subsequently decreased during disease progression of AKI, CKD, and diabetic nephropathy. These and other kidney diseases force patients, particularly pediatric patients, to face dialysis, surgical procedures, and ultimately, transplant. To summarize the current literature for researchers and pediatric nephrologists, this review aims to expound HA and elucidate its paradoxical effects in multiple kidney diseases using studies that emphasize HA molecular weight when available.

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Hyaluronidase 1 and hyaluronidase 2 are required for renal hyaluronan turnover

Cited by 12 publications

References 31 publications

Respective roles of hyaluronidases 1 and 2 in endogenous hyaluronan turnover

Respective roles of hyaluronidases 1 and 2 in endogenous hyaluronan turnover

Hyaluronidase 2 (HYAL2) is expressed in endothelial cells, as well as some specialized epithelial cells, and is required for normal hyaluronan catabolism

Hyaluronan, a double-edged sword in kidney diseases

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