Effect of vasopressin on the expression of genes for key enzymes of interstitial hyaluronan turnover and concentration ability in WAG rat kidneys

In mammals, arginine-vasopressin (AVP) is a major hormone involved in the regulation of renal water reabsorption, acting via an increase in the osmotic permeability of the collecting duct epithelium. The AVP-induced intracellular events include, as an essential step, the trafficking of the vesicles containing the water channels, aquaporin-2, to the apical plasma membrane of the collecting duct principal cells. The interstitium of the renal inner medulla contains abundant linear negatively charged glycosaminoglycan hyaluronan (HA), which affects the water flow depending on their polymeric state. Using real-time RT-PCR, we tested the assumption that the renal hyaluronan may be involved in the longterm vasopressin effect on water reabsorption. The expression of the genes encoding hyaluronan synthase-2 (Has2) and hyaluronidase-1, 2 (Hyal1, Hyal2) in the kidneys of Wistar Albino Glaxo (WAG) was studied. Has2 mRNA content was the highest in the kidney papilla of the hydrated rats. The V2 receptor-selective vasopressin analog dDAVP (100 μg/kg bw, ip, twice a day for 2 days) induced a considerable decrease in Has2 mRNA content in the papilla with less pronounced changes in the cortex. In contrast to Has2, dDAVP treatment caused a significant increase in Hyal1 and Hyal2 mRNA content in the renal papilla. There was a good fit between Hyal1 and Hyal2 transcriptional level and changes in hyaluronidase activity in the renal tissue. It was suggested that vasopressin is able to inhibit the synthesis of hyaluronan and concomitantly promotes its degradation in the renal papilla interstitium, thereby facilitating water flow between elements of the renal countercurrent system. The implications for this effect are discussed in the context of the literature data.

1. Agre P. Molecular physiology of water transport: aquaporins. Biol. Cell. 1997;89:255-257.

2. Agre P. Nobel lecture. Aquaporin water channels. Biosci. Rep. 2004;24: 127-163.

3. Asteriou T., Vincent J.C., Tranchepain F., Deschrevel B. Inhibition of hyaluronan hydrolysis catalysed by hyaluronidase at high substrate concentration and low ionic strength. Matrix Biol. 2006;25:166-174.

4. Bartolo R.C., Donald J.A. The distribution of renal hyaluronan and the expression of hyaluronan synthases during water deprivation in the Spinifex hopping mouse. Notomys alexis. Comp. Biochem. Physiol. Part A. Mol. Integr. Physiol. 2007;148:853-860.

5. Bookout A.L., Cummins C.L., Mangelsdorf D.J., Pesola J.M., Kramer M.F. High- throughput real-time quantitative reverse transcription PCR. Curr. Protoc. Mol. Biol. 2006;Chapter 15:Unit 15.8.

6. Brooks H.L., Ageloff S., Kwon T.-H., Brandt W., Terris J.M., Seth A., Michea L., Nielsen S., Fenton R., Knepper M. cDNA array identification of genes regulated in rat renal medulla in response to vasopressin infusion. Am. J. Physiol. Renal. Physiol. 2003;284:F218-F228.

7. Bulger R.E. Composition of renal medullary tissue. Kidney Int. 1987; 31:556-561.

8. Comper W.D., Laurent T.C. Physiological function of connective tissue polysaccaharides. Physiol. Rev. 1978;58:265-315.

9. Csoka A.B., Frost G.I., Stern R. The six hyaluronidase-like genes in the human and mouse genomes. Matrix Biol. 2001;20:499-508.

10. Day T.D. The permeability of the interstitial connective tissue and the nature of the interfibrillary substance. J. Physiol. 1952;177:1-8.

11. Ecelbarger C.A., Chon C.L., Lolait S.J., Knepper M.A., DiGiovanni S.R. Evidence for dual signaling pathways for V2 vasopressin receptor in rat inner medullary collecting duct. Am. J. Physiol. 1996; 270:623-633.

12. Ericsson M., Stern R. Chain gangs: new aspects of hyaluronan metabolism. Biochem. Res. Int. 2012. DOI 10.1155/2012/893947

13. Ginetzinsky A.G. Role of hyaluronidase in the reabsorption of water in renal tubules (The mechanism of action of antidiuretic hormone). Nature. 1958;182:1218-1219.

14. Hansell P., Göranson V., Odlind C., Gerdin B., Hallgern R. Hyaluronan content in the kidney in different states of body hydration. Kidney Int. 2000;58:2061-2068.

15. Harada H., Takahashi M. CD44-dependent intracellular and extracellular catabolism of hyaluronic acid by nyaluronidase-1 and -2. J. Biol. Chem. 2007;282:5597-5607.

16. Hedbys B.O. Corneal resistance to the flow of water after enzymatic digestion. Exptl. Eye. Res. 1963;2:112-121.

17. Itano N., Kimata K. Expression cloning and molecular characterization of HAS protein, a eukaryotic hyaluronan synthase. J. Biol. Chem. 1996;271:9875-9878.

18. Ivanova L.N. To the question on hyaluronidase role in urine production. Byulleten eksperimentalnoy biologii i meditsiny = Bulletin of Experimental Biology and Medicine. 1958;45:22-27.

19. Ivanova L.N., Goryunova T.E., Nikiforovskaya L.F., Tishchenko N.I. Hyaluronate hydrolase activity and glycosaminoglycans in the Brattleboro rat kidney. Ann. N.Y. Acad. Sci. 1982;394:503-508.

20. Ivanova L.N., Goryunova T.E., Nikiforovskaya L.F., Tishchenko N.I. Distribution and activity of hyaluronate hydrolases in the kidney and their reaction to ADH. Eds R. Dzurik, B. Lichardus, W. Guder. Kidney metabolism and function. Dortrecht:Martinus Nyhoff, 1985.

21. Ivanova L.N., Vinogradov V.V. Histochemical features of renal medullar interstitial mucopolisacharides. Arkhiv anatomii, gistologii i embriologii = Archives of anatomy, histology and embryology. 1962; 43:18-23.

22. Ivanova L.N., Melidi N.N. Effects of vasopressin on hyaluronate hydrolase activities and water permeability in the frog urinary bladder. Pflugers Arch – Eur. J. Physiol. 2001;443:72-77.

23. Jacobson A., Brink J., Briskin M.J., Spicer A.P., Heldin P. Expression of human hyaluronan synthases in response to external stimuli. Biochem. J. 2000;348:29-35.

24. Jedrzejas M.J., Stern R. Structures of vertebrate hyaluronidases and their unique enzymatic mechanism of hydrolysis. Proteins. 2005;61: 227-238.

25. Knepper M.A., Saidel G.M., Hascall V.C., Dwyer T. Concentration of solutes in the renal inner medulla: interstitial hyaluronan as a mechanoosmotic transducer. Am. J. Physiol. Renal. Physiol. 2003;284: 433-446.

26. Lee J.Y., Spicer A.P. Hyaluronan: a multifunctional, megaDalton, stealth molecule. Curr. Opin Cell. Biol. 2000;12:581-588.

27. Natochin Y.V. Hyaluronidase secretion in the kidney of different vertebrates. Byulleten eksperimentalnoy biologii i meditsiny = Bulletin of Experimental Biology and Medicine. 1959;48:10-16.

28. Nielsen S., Frokler J., Marples D., Kwon T.-H., Agre P., Knepper M. Aquaporins in the kidney: from molecules to Medicine. Physiol. Rev. 2001;82:205-244.

29. Noda Y., Sasaki S. Trafficking mechanism of water channel aquaporin-2. Biol. Cell. 2005;97:885-892.

30. Pinter G.G., Shohet J.L. An inner medullary concentrating process activated by renal pelviccalyceal muscle contractions: assessment and hypothesis. J. Nephron. Physiol. 2009;113:1-6.

31. Preston B.N., Davies M., Ogston A.G. The composition and physicochemical properties of hyaluronate acids prepared from ox synovial fluid and from mesothelioma. Biochem. J. 1965;96:449-471.

32. Rinschen M.M., Yu M.-J.G., Boja J.D., Hoffert T., Pisitcun T., Knepper M.A. Quantitative phosphoproteomic analysis reveals vasopressin V2-receptor – dependent signaling pathway in renal collecting duct cells. PNAS. 2010;107:3882-3887.

33. Rügheimer L., Johnsson C., Maric C., Hansell P. Hormonal regulation of renomedullary hyaluronan. Acta Physiol. 2008;193:191-198.

34. Rügheimer L., Olerud L., Johnsson C., Takahashi T., Shimizu K., Hansell P. Hyaluronan synthases and hyaluronidases in the kidney during changes in hydration status. J. Matrix Biol. 2009;28:390-395.

35. Spicer A.P., McDonald J.A. Characterization and molecular evolution of a vertebrate hyaluronan synthase gene family. J. Biol. Chem. 1998;273:1923-1932.

36. Stern R. Devising a pathway for hyaluronan catabolism: are we there yet? Glycobiology. 2003;13:105R-115R.

37. Stridh S., Palm F., Hansell P. Renal interstitial Hyaluronan: functional aspects during normal and pathological conditions. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2012;302:R1235-R1249.

38. Takahashi T., Ikegami-Kawai M., Okuda R., Susuki K. A fluorimetric Morgan-Elson assay method for hyaluronidase activity. Anal. Biochem. 2003;322:257-261.

39. Uawithya P., Pisitkun T., Ruttenberg B.E., Knepper M.A. Transcriptional profiling of native inner medullary collecting duct cells from rat kidney. Physiol. Genomics. 2008;32:229-253.

40. Zaks M.G., Titova M.M. Histological and histochemical changes in rat kidney under hydration and antidiuresis. Arkhiv anatomii, gistologii i embriologii = Archives of anatomy, histology and embryology. 1959;37:19-24.