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Renal Hyaluronan Content During Experimental Uncontrolled Diabetes in Rats
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
2008 (English)In: Journal of Physiology and Pharmacology, ISSN 0867-5910, Vol. 59, no 1, 115-128 p.Article in journal (Refereed) Published
Description
Abstract [en]

With diabetes mellitus, the ability of the kidneys to maintain fluid balance is affected. Hyperglycaemia increases production of hyaluronan in cultured kidney cells implying that diabetes promotes induction of hyaluronan in the kidney. The aim of the present study was to determine if the interstitial matrix component hyaluronan is differently distributed within the kidney in diabetic rats compared to non-diabetic rats. Furthermore, to test if diabetic rats are able to respond with diuresis upon a hypotonic fluid load. The normal heterogeneous intrarenal distribution of hyaluronan was confirmed in non-diabetic control rats, with 60-fold more in the papilla than in the cortex. In diabetic animals, the cortical hyaluronan was unaffected but the papillary hyaluronan content was 3-fold higher than in non-diabetic rats. This increase correlated with a more than three-fold induction of the papillary hyaluronansynthase 2 mRNA expression. In non-diabetic animals, 2 h water loading increased papillary hyaluronan (+93%) and diuresis (17-fold). In diabetic animals, baseline diuresis was 8-fold higher than in non-diabetic animals, which correlated with hyperglycaemia, glucosuria and proteinuria. Water loading in diabetic animals did not further increase papillary hyaluronan or diuresis: the urine flow rate decreased. To conclude, papillary hyaluronan is elevated in diabetic rats, which coincides with induction of hyaluronan-synthase 2 mRNA, hyperglycaemia, glucosuria, proteinuria and overt diuresis. The inability to respond to a water load with further diuresis may be related to the already elevated papillary hyaluronan and the inability to change hyaluronan during water loading.

Place, publisher, year, edition, pages
2008. Vol. 59, no 1, 115-128 p.
Keyword [en]
diabetes, hyaluronan, kidney, water loading, diuresis
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-97209ISI: 000254635300010PubMedID: 18441392OAI: oai:DiVA.org:uu-97209DiVA: diva2:172038
Available from: 2008-04-30 Created: 2008-04-30 Last updated: 2017-01-04Bibliographically 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.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 351
Keyword
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
Identifiers
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
Opponent
Supervisors
Available from: 2008-04-30 Created: 2008-04-30Bibliographically approved

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