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Gene Review

Umod  -  uromodulin

Rattus norvegicus

Synonyms: THP, Tamm-Horsfall urinary glycoprotein, Uromodulin
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Disease relevance of Umod

  • We suggest a potential involvement of THP in the renal functional changes associated with hypothyroidism [1].
  • We determined whether l-arg supplementation safeguards the renal epithelial cell damage induced by hyperoxaluria with excretion of urinary marker enzymes and lithogenic salts with special reference to Tamm-Horsfall glycoprotein (THP) [2].
  • These findings also suggest that restriction of dietary salt may be beneficial in cast nephropathy in multiple myeloma and recurrent nephrolithiasis, two diseases in which THP can play an important pathogenetic role [3].
  • THP inhibited catalepsy intensity with an ED(50) of 0.38 mg/kg, and increased its onset latency with an ED(50) of 0.52 mg/kg [4].
  • Multiple pathways for escape of urinary THP from tubules were demonstrated and included tubular ruptures and necrosis, forniceal tears, and venous polyps [5].

Psychiatry related information on Umod

  • Pretreatment of rats with a single dose of THP or P4 (50 micrograms/kg) significantly attenuated the elevation of plasma adrenocorticotropin (ACTH) and serum corticosterone after emotional stress; both steroids were, however, less potent than a similar dose of DEX [6].
  • Post-mortem histological analysis revealed that buspirone-treated rats reduced alcohol consumption by 83% if THP had been microinjected into substantia nigra; by 60% if given in the nucleus accumbens-preoptic area; and by 34% when injected into the medial lemniscus-zona incerta [7].

High impact information on Umod

  • The unique N-terminal domain of rat THP (unique-THP, Pro29-Gln174) shows four conserved epidermal growth factor motifs, three in tandem and one in reverse orientation [8].
  • GP-2/THP gene family encodes self-binding glycosylphosphatidylinositol-anchored proteins in apical secretory compartments of pancreas and kidney [8].
  • These include a zona pellucida binding domain, which is present in a number of proteins such as the zona pellucida sperm binding proteins, and uromodulin, In addition, there is a repeat of a motif called CUB domain, which exists in a number of genes involved in development and differentiation such as bone morphogenetic protein 1 (BMP1) [9].
  • Vitamin E supplement prevented the loss of OPN and THP in renal tissues by EG and the reduction in their levels in the urine [10].
  • The beneficial effect of vitamin E in reducing CaOx accumulation is due to attenuation of tubular cell death and enhancement of the defensive roles of OPN and THP [10].

Chemical compound and disease context of Umod

  • In the presence of caffeine, THP inhibited catalepsy intensity with an ED(50) of 0.19 mg/kg, and prolonged the latency with an ED(50) of 0.30 mg/kg [4].
  • Thus, it appears that THP acts through DA D2 receptor antagonism to induce hypotension and bradycardia in rats [11].
  • The possibility of more than one urinary protein being simultaneously associated with calcium oxalate (CaOx) crystallization in vivo was investigated by examining the localization of Tamm-Horsfall protein (THP) and osteopontin (Opn) in a rat model of nephrolithiasis [12].
  • Intravenous administration of THP (1-10 mg/kg) or haloperidol (0.5-1.25 mg/kg) produced hypotension, bradycardia and increased DA release in the striatum [11].
  • Antidiuretic hormone treatment in (3) slightly lowered THP excretion (287 +/- 53 vs. 367 +/- 41 micrograms/day per 100 g body weight; p less than 0.005), whereas high-protein diet, in experiment (4), led to a 50% increase in THP excretion (446 +/- 57 vs. 304 +/- 79 micrograms/day per 100 g body weight; p less than 0.001) [13].

Biological context of Umod


Anatomical context of Umod

  • However, whereas CORT and P4 influenced the ADX-induced increase in the transcription of both types of corticosteroid receptors in the hippocampus, these were unaffected by THP [6].
  • Administration of 1 mg of THP, CORT, or P4 to adrenalectomized (ADX) rats attenuated the increase in AVP mRNA levels in the ventromedial subdivision of the hypothalamic paraventricular nucleus (PVN), as compared with vehicle-treated ADX rats [6].
  • Urinary casts containing THP were detected not only distal to the site of THP synthesis in cells of the ascending limbs of the loop of Henle, but also in more proximal portions of the nephron, suggesting retrograde intratubular movement of urine [5].
  • The distribution of Tamm-horsfall protein (THP) within nephrons and in the renal interstitium of the kidney was examined in rats after unilateral ureteral ligation [5].
  • No morphologic evidence suggesting passage of THP across Bowman's capsule of these glomeruli was found [5].

Associations of Umod with chemical compounds

  • To further confirm that changes were specific for THP and not merely the consequence of reduced kidney growth, the abundance of barttin, another distal tubular protein related to chloride transport, was tested as well [1].
  • In spectrophotometric crystallization assay system, l-arg supplemented rat THP showed inhibition in nucleation and aggregation phases, whereas EG-treated rat THP showed promotion of both calcium oxalate nucleation and aggregation phases [2].
  • BACKGROUND: Tamm-Horsfall glycoprotein (THP) is a unique protein that is produced exclusively by cells of the thick ascending limb of Henle's loop (TALH) [3].
  • CONCLUSIONS: An increase in dietary salt and the loop diuretic, furosemide, increased expression of THP in the rat [3].
  • In contrast to the glucocorticoids, THP and P4 failed to decrease plasma ACTH levels in rats deprived of endogenous steroids [6].

Analytical, diagnostic and therapeutic context of Umod

  • Western blotting indicated a 40% reduction in renal THP content ( P<0.005), and daily urinary THP excretion was 68% lower than in controls ( P<0.05) [1].
  • Isolation and purification of THP was carried in rat urine and were subjected to spectrophotometric crystallization assay and calcium-(14)C-oxalate binding studies [2].
  • Immunohistochemistry demonstrated expression of MHC II, COX-2, THP, and BSC-1/NKCC2 proteins in normally developing TALH cells [14].
  • These data demonstrate that THP and some other TIQs can act as dopamine antagonists in radioreceptor assays, in cell culture and in vivo [18].
  • Glomerular dysfunction in several models-spontaneously hypertensive rats (SHR), aging Sprague-Dawley (SD) rats, rats with adriamycin nephropathy (ADR), and rats subjected to subtotal nephrectomy (NX)-was characterized by immunomorphometric analysis after injection of anti-THP antibodies [19].


  1. Selectively reduced expression of thick ascending limb Tamm-Horsfall protein in hypothyroid kidneys. Schmitt, R., Kahl, T., Mutig, K., Bachmann, S. Histochem. Cell Biol. (2004) [Pubmed]
  2. Oral L-arginine supplementation ameliorates urinary risk factors and kinetic modulation of Tamm-Horsfall glycoprotein in experimental hyperoxaluric rats. Pragasam, V., Kalaiselvi, P., Sumitra, K., Srinivasan, S., Varalakshmi, P. Clin. Chim. Acta (2005) [Pubmed]
  3. Dietary salt regulates expression of Tamm-Horsfall glycoprotein in rats. Ying, W.Z., Sanders, P.W. Kidney Int. (1998) [Pubmed]
  4. Caffeine and muscarinic antagonists act in synergy to inhibit haloperidol-induced catalepsy. Moo-Puc, R.E., Góngora-Alfaro, J.L., Alvarez-Cervera, F.J., Pineda, J.C., Arankowsky-Sandoval, G., Heredia-López, F. Neuropharmacology (2003) [Pubmed]
  5. Renal localization of Tamm-horsfall protein in unilateral obstructive uropathy in rats. Dziukas, L.J., Sterzel, R.B., Hodson, C.J., Hoyer, J.R. Lab. Invest. (1982) [Pubmed]
  6. The neurosteroid tetrahydroprogesterone attenuates the endocrine response to stress and exerts glucocorticoid-like effects on vasopressin gene transcription in the rat hypothalamus. Patchev, V.K., Hassan, A.H., Holsboer, D.F., Almeida, O.F. Neuropsychopharmacology (1996) [Pubmed]
  7. Buspirone alters alcohol drinking induced in rats by tetrahydropapaveroline injected into brain monoaminergic pathways. Privette, T.H., Hornsby, R.L., Myers, R.D. Alcohol (1988) [Pubmed]
  8. GP-2/THP gene family encodes self-binding glycosylphosphatidylinositol-anchored proteins in apical secretory compartments of pancreas and kidney. Fukuoka, S., Freedman, S.D., Yu, H., Sukhatme, V.P., Scheele, G.A. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  9. Cloning and uterus/oviduct-specific expression of a novel estrogen-regulated gene (ERG1). Chen, D., Xu, X., Zhu, L.J., Angervo, M., Li, Q., Bagchi, M.K., Bagchi, I.C. J. Biol. Chem. (1999) [Pubmed]
  10. Vitamin E attenuates crystal formation in rat kidneys: roles of renal tubular cell death and crystallization inhibitors. Huang, H.S., Chen, J., Chen, C.F., Ma, M.C. Kidney Int. (2006) [Pubmed]
  11. DL-tetrahydropalmatine-produced hypotension and bradycardia in rats through the inhibition of central nervous dopaminergic mechanisms. Chueh, F.Y., Hsieh, M.T., Chen, C.F., Lin, M.T. Pharmacology (1995) [Pubmed]
  12. Localization of tamm-horsfall protein and osteopontin in a rat nephrolithiasis model. Gokhale, J.A., Glenton, P.A., Khan, S.R. Nephron (1996) [Pubmed]
  13. Tamm-Horsfall protein excretion during chronic alterations in urinary concentration and protein intake in the rat. Bachmann, S., Dawnay, A.B., Bouby, N., Bankir, L. Renal physiology and biochemistry. (1991) [Pubmed]
  14. Neonatal RAS inhibition changes the phenotype of the developing thick ascending limb of Henle. Lasaitiene, D., Friberg, P., Sundelin, B., Chen, Y. Am. J. Physiol. Renal Physiol. (2004) [Pubmed]
  15. Impaired absorption of chlorpromazine in rats given trihexyphenidyl. Rivera-Calimlim, L. Br. J. Pharmacol. (1976) [Pubmed]
  16. Effects of pirarubicin, an antitumor antibiotic, on the cardiovascular system. Hirano, S., Agata, N., Hara, Y., Iguchi, H., Shirai, M., Tone, H., Urakawa, N. Cancer Chemother. Pharmacol. (1991) [Pubmed]
  17. Effect of progesterone, testosterone and their 5 alpha-reduced metabolites on GFAP gene expression in type 1 astrocytes. Melcangi, R.C., Riva, M.A., Fumagalli, F., Magnaghi, V., Racagni, G., Martini, L. Brain Res. (1996) [Pubmed]
  18. In vivo and in vitro effects of tetrahydroisoquinolines and other alkaloids on rat pituitary function. Britton, D.R., Rivier, C., Shier, T., Bloom, F., Vale, W. Biochem. Pharmacol. (1982) [Pubmed]
  19. Immunomorphometric studies of proteinuria in individual deep and superficial nephrons of rats. Hoyer, J.R., Fogo, A.B., Terrell, C.H., Delaney, M.M. Lab. Invest. (2000) [Pubmed]
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