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Gene Review

Klk1c8  -  kallikrein 1-related peptidase C8

Rattus norvegicus

Synonyms: Glandular kallikrein-8, KLK8, Klk-8, Klk1b21, Klk6, ...
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Disease relevance of Klk6_predicted

  • Proteomic analysis reveals alterations in the renal kallikrein pathway during hypoxia-induced hypertension [1].
  • These data indicate that EH induces changes in renal protein expression consistent with impairment of vasodilation mediated by the kallikrein-kallistatin pathway and vascular hypertrophy [1].
  • Reversal of renal fibrosis, inflammation, and glomerular hypertrophy by kallikrein gene delivery [2].
  • The kallikrein/kinin system is beneficial in ischemia/reperfusion injury in heart, controversial in brain, but detrimental in lung, liver, and intestine [3].
  • Two weeks after adenovirus injection, salt-induced glomerular sclerosis, tubular protein cast formation, and monocyte/ macrophage accumulation in the kidney were notably reversed by kallikrein [2].

High impact information on Klk6_predicted


Biological context of Klk6_predicted

  • These proteinases correspond to the products of the RSKG-7 and the rGK8 genes, as shown by the comparison of their partial amino-acid sequence with that deduced from nucleotide sequences [6].
  • Such involvement would suggest that kallikrein is not only potentially involved in an important function of brain development, but also available for studies on regenerative medicine for neurons [7].
  • The enzymatic activity of renal tissue kallikrein (active and total; specifically antagonized by anti-tissue kallikrein antibodies), increased from 4 to 52 weeks in SHR when compared to normotensive Wistar Kyoto (WKY) rats; this increase was associated with a significant increase in blood pressure [8].
  • Consequently, a Charon 4A rat genomic library was screened for kallikrein genes by hybridization with rat tissue kallikrein cDNA [9].

Anatomical context of Klk6_predicted

  • Growth-stimulating Effect of Kallikrein on Rat Neural Stem Cells [7].
  • In conclusion, vascular kinin-mediated symptoms observed during oedematous pancreatitis in the rat are caused by the action of tissue kallikrein in the pancreas whereas an involvement of plasma kallikrein seems to be unlikely [10].
  • This suggests that a tissue kallikrein and also a trypsin-like enzyme or perhaps plasma kallikrein are present in rat uterus [11].
  • In Western blot analyses, a specific monoclonal antibody to tissue kallikrein (V4D11) identifies GH3-secreted kallikrein as a approximately 39,000 Da protein, slightly larger than approximately 38,000 Da kallikreins of submandibular gland, mouse anterior pituitary cells (AtT 20) or rodent neuroblastoma X glioma hybrid cells (NG108) [12].
  • Nitrite and kallikrein levels in dental pulp tissue were higher in diabetic rats 30 days after STZ treatment than in controls, while only nitrite were decreased 90 after of STZ treatment [13].

Associations of Klk6_predicted with chemical compounds

  • Since bradykinin B(2)-receptor antagonist, Hoe140, did not suppress the growth-stimulating effect, kallikrein-mediated kinin release does not appear to be involved in this effect [7].
  • Kallikrein gene delivery also dramatically reduced collagens I, III, and IV and reticulin deposition, accompanied by a decline in myofibroblast accumulation and transforming growth factor-beta(1) expression [2].
  • In addition, kallikrein protected against salt-induced renal injury by diminishing urinary protein and blood urea nitrogen levels [2].
  • These protective actions of kallikrein were abolished by icatibant, indicating a B2 receptor-mediated event [2].
  • Renal kallikrein is secreted by the distal connecting tubular cells and all kallikrein-kinin system components are distributed along the collecting ducts in the distal nephron [14].

Analytical, diagnostic and therapeutic context of Klk6_predicted

  • Expression in Escherichia coli was detected by direct radioimmunoassay, and recombinant kallikrein of 36 kDa was identified by Western-blot analysis using both polyclonal and monoclonal antibodies to rat tissue kallikrein, and by autoradiography of 14C-labelled L-amino acid-labelled-protein synthesis in the presence of rifampicin [15].
  • A rat tissue kallikrein cDNA probe, 534 bases in length and complementary to the 3' end of kallikrein mRNA was first used in Northern blot analysis to demonstrate the existence of tissue kallikrein mRNA in rat kidney [16].


  1. Proteomic analysis reveals alterations in the renal kallikrein pathway during hypoxia-induced hypertension. Thongboonkerd, V., Gozal, E., Sachleben, L.R., Arthur, J.M., Pierce, W.M., Cai, J., Chao, J., Bader, M., Pesquero, J.B., Gozal, D., Klein, J.B. J. Biol. Chem. (2002) [Pubmed]
  2. Reversal of renal fibrosis, inflammation, and glomerular hypertrophy by kallikrein gene delivery. Bledsoe, G., Shen, B., Yao, Y., Zhang, J.J., Chao, L., Chao, J. Hum. Gene Ther. (2006) [Pubmed]
  3. Early activation of bradykinin B2 receptor aggravates reactive oxygen species generation and renal damage in ischemia/reperfusion injury. Chiang, W.C., Chien, C.T., Lin, W.W., Lin, S.L., Chen, Y.M., Lai, C.F., Wu, K.D., Chao, J., Tsai, T.J. Free Radic. Biol. Med. (2006) [Pubmed]
  4. Purification and characterization of a kallikrein-like T-kininogenase. Xiong, W., Chen, L.M., Chao, J. J. Biol. Chem. (1990) [Pubmed]
  5. Identification of tissue kallikrein in brain and in the cell-free translation product encoded by brain mRNA. Chao, J., Woodley, C., Chao, L., Margolius, H.S. J. Biol. Chem. (1983) [Pubmed]
  6. Substrate specificity of two kallikrein family gene products isolated from the rat submaxillary gland. Elmoujahed, A., Gutman, N., Brillard, M., Gauthier, F. FEBS Lett. (1990) [Pubmed]
  7. Growth-stimulating Effect of Kallikrein on Rat Neural Stem Cells. Kizuki, K., Ookubo, R., Iwadate, H., Sada, K. Yakugaku Zasshi (2006) [Pubmed]
  8. An ontogenic study of renal tissue kallikrein in Okamoto spontaneously hypertensive rats: comparisons with human hypertensive nephropathy. Figueroa, C.D., Bhoola, K.D., MacIver, A.G., Mackenzie, J.C. Nephrol. Dial. Transplant. (1992) [Pubmed]
  9. Immunological identification of rat tissue kallikrein cDNA and characterization of the kallikrein gene family. Gerald, W.L., Chao, J., Chao, L. Biochim. Biophys. Acta (1986) [Pubmed]
  10. Involvement of tissue kallikrein but not plasma kallikrein in the development of symptoms mediated by endogenous kinins in acute pancreatitis in rats. Griesbacher, T., Rainer, I., Tiran, B., Evans, D.M. Br. J. Pharmacol. (2002) [Pubmed]
  11. Kininogenase activity in rat uterus homogenates. Marin-Grez, M., Schaechtelin, G., Hermann, K. Hoppe-Seyler's Z. Physiol. Chem. (1982) [Pubmed]
  12. Identification of latent tissue kallikrein, prolactin and growth hormone secretion in GH3 pituitary cells using modified radioimmunoassays. Chao, J., Chao, L. Mol. Cell. Endocrinol. (1988) [Pubmed]
  13. Diabetes and its effects on dental pulp. Catanzaro, O., Dziubecki, D., Lauria, L.C., Ceron, C.M., Rodriguez, R.R. Journal of oral science (2006) [Pubmed]
  14. A missing link between a high salt intake and blood pressure increase. Katori, M., Majima, M. J. Pharmacol. Sci. (2006) [Pubmed]
  15. Purification and characterization of recombinant tissue kallikrein from Escherichia coli and yeast. Wang, J., Chao, J., Chao, L. Biochem. J. (1991) [Pubmed]
  16. Renal kallikrein mRNA localization by in situ hybridization. Xiong, W., Chao, L., Chao, J. Kidney Int. (1989) [Pubmed]
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