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Hyaluronan synthases and hyaluronidases in the kidney during changes in hydration status
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrativ Fysiologi.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrativ Fysiologi.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
School of Pharmaceutical Sciences, Ohu University, Koriyama, Japan.
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2009 (English)In: Matrix Biology, ISSN 0945-053X, E-ISSN 1569-1802, Vol. 28, no 7, 390-395 p.Article in journal (Refereed) Published
Abstract [en]

Hyaluronan is a large glycosaminoglycan that is abundant in the   interstitium of the renal medulla/papilla. Papillary hyaluronan   increases during hydration and decreases during dehydration. Due to its   gel properties and ability to retain large volumes of water, hyaluronan   plays a role in renal water handling by affecting the permeability   characteristics of the papillary interstitium. The focus of the present   investigation was the regulation of hyaluronan metabolism in the   kidney, especially during variations in hydration status.   In control papillas, HAS 2 mRNA was heavily expressed and HAS 1 and 3   mRNA were weakly distributed. HYALs 1-3 mRNA were found at high   expression and HYAL 4 was only weakly expressed. in hydrated animals,   the diuretic response (12-fold) was followed by a 58% elevation in   papillary hyaluronan and a 45% reduction in the excreted urinary   hyaluronidase activity. No difference was determined in HAS 1-3 mRNA or   HYAL 1, 3-4 mRNA expression, suggesting a change in activity rather   than amount of protein. In dehydrated animals, antidiuresis was   followed by a 22% reduction in papillary hyaluronan and a 62% elevation   in excreted urinary hyaluronidase activity. Plasma vasopressin was   2.8-fold higher in dehydrated vs. hydrated rats.   In conclusion, HAS 2 appears a major contributor to the baseline levels   of hyaluronan. Reduced HAS 2 gene expression and increased excreted   urinary hyaluronidase activity during dehydration contribute to the   reduced amount of hyaluronan and to antidiuretic response.

Place, publisher, year, edition, pages
2009. Vol. 28, no 7, 390-395 p.
Keyword [en]
Hyaluronidase, Hyaluronan synthase, Hyaluronan, Kidney, Hydration, Dehydration
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-97207DOI: 10.1016/j.matbio.2009.07.002ISI: 000272102000003PubMedID: 19635555OAI: oai:DiVA.org:uu-97207DiVA: diva2:172036
Available from: 2008-04-30 Created: 2008-04-30 Last updated: 2011-12-05Bibliographically approved
In thesis
1. Kidney Hyaluronan: Regulatory Aspects During Different States of Body Hydration, Nephrogenesis & Diabetes
Open this publication in new window or tab >>Kidney Hyaluronan: Regulatory Aspects During Different States of Body Hydration, Nephrogenesis & Diabetes
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The kidney regulates the excretion of water and electrolytes, which maintains homeostasis and enables control of arterial blood pressure. Hyaluronan, a large negatively charged interstitial glucosaminoglycan, is heterogeneously distributed within the kidney, primarily found in the medulla.

Medullary hyaluronan content changes depending on the state of body hydration and plays a part in fluid regulation through its water binding and viscoelastic properties.

The aim of this thesis was to provide new insight into the regulation of intrarenal hyaluronan during different states of body hydration, during completion of kidney development, and during diabetes mellitus.

Dehydration reduces medullary interstitial hyaluronan in parallel with reduced hyaluronan synthase 2 gene expression and increased urinary hyaluronidase activity. Acute hydration results in an increase in medullary hyaluronan, an increase that requires nitric oxide and prostaglandins. Urinary hyaluronidase activity decreases during hydration. The elevation of hyaluronan is important for reducing water permeability of the interstitium i.e. favoring diuresis.

Changes in hyaluronan concentration constitute a morphoregulatory pathway that plays a key role in nephrogenesis. The reduction in neonatal hyaluronan depended on an angiotensin II mediated process that does not appear dependent on lymph vessel formation. If angiotensin II is blocked with an ACE inhibitor, hyaluronan accumulates, which results in structural and functional abnormalities in the kidney.

Renomedullary hyaluronan is elevated during uncontrolled diabetes, which coincides with induction of hyaluronan synthase 2 mRNA, hyperglycemia, glucosuria, proteinuria and overt diuresis. The levels of hyaluronan are probably at a terminus ad quem as no further response was seen during hydration. The higher interstitial expression of hyaluronan during diabetes may be involved in the progression of diabetic nephropathy.

This thesis in physiology provides new mechanistic insights into the regulation of renal hyaluronan during various aspects of fluid handling.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 64 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 351
Physiology, hyaluronan, kidney, dehydration, hydration, diabetes, nephrogenesis, renomedullary interstitial cells, CD44, hyaluronan synthase, hyaluronidase, vasopressin, nitric oxide, prostaglandins, glucocorticoids, angiotensin II, diuresis, lymph vessel, podoplanin, Fysiologi
urn:nbn:se:uu:diva-8724 (URN)978-91-554-7199-6 (ISBN)
Public defence
2008-05-23, B42, Biomedical center, BMC, Husargatan 3, Uppsala, 13:15
Available from: 2008-04-30 Created: 2008-04-30Bibliographically approved

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