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Gene Review

Nppc  -  natriuretic peptide type C

Mus musculus

Synonyms: C-type natriuretic peptide, CNP, Cnp, lbab, natriuretic peptide precursor C
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Disease relevance of Nppc

  • The Nppc(-/-) mice show severe dwarfism as a result of impaired endochondral ossification [1].
  • We determined that Nppc is induced in renal tubular epithelia and then in interstitial myofibroblasts after unilateral ureteral obstruction (UUO) [2].
  • These findings suggest that Wnt-4 stimulates Nppc in a TCF/LEF-dependent manner after renal injury and thus may contribute to limiting renal fibrosis [2].
  • Using cultured fetal mouse tibias, an in vitro model system of endochondral ossification, we also demonstrated that CNP cannot increase the longitudinal bone growth, and chondrocytic proliferation and hypertrophy, and cartilage matrix synthesis in Prkg2(-/-) mice [3].
  • Genomic sequences encoding mouse C-type natriuretic peptide (CNP) were isolated from bacteriophage libraries and characterized by restriction enzyme and sequence analysis [4].

Psychiatry related information on Nppc

  • In contrast, the ability of CNP to stimulate cGMP production was significantly increased after 14 days of water deprivation [5].
  • Cnp exposure was found to prolong the response latency to a nociceptive thermal stimulus (hot plate) [6].

High impact information on Nppc


Chemical compound and disease context of Nppc

  • Addition of Rp-8-[(4-chlorophenyl)thio]-cGMPS triethylamine (an inhibitor of cGMP-dependent protein kinase, 5 x 10(-6) M) blocked SNAP or the effect of CNP in control mice but not in hypertrophy, indicating the cGMP-dependent kinase (PKG) may not mediate the actions of cGMP induced by NO or CNP in the hypertrophic state [9].
  • The monoclonal antibody immunoprecipitated CNP enzyme activity from extracts of C6 glioma cells [10].
  • Accordingly, we investigated whether CNP infusion attenuates bleomycin (BLM)-induced pulmonary fibrosis in mice [11].
  • CNP infusion significantly attenuated BLM-induced pulmonary fibrosis, as indicated by significant decreases in Ashcroft score and lung hydroxyproline content [11].

Biological context of Nppc

  • However, given that Prkg2(-/-) mice differ from CNP-deficient mice (Nppc(-/-) mice) in the growth plate histology, which downstream mediator(s) of cGMP play key roles in the process is still an enigma [3].
  • Analysis of allele distributions in interspecific back-cross and recombinant inbred strains assigned Nppc to chromosome 1 [4].
  • The mouse CNP gene (Nppc) comprised at least two exons and one intron and included several cis-regulatory elements in the 5'-flanking sequence [4].
  • CNP gene expression is activated by Wnt signaling and correlates with Wnt4 expression during renal injury [2].
  • However, the efficacy of CNP for vasorelaxation was markedly diminished compared with wild-type RRA [12].

Anatomical context of Nppc

  • Targeted expression of CNP in the growth plate chondrocytes can rescue the skeletal defect of Nppc(-/-) mice and allow their prolonged survival [1].
  • Histological examination revealed an increase in the height of the proliferative and hypertrophic chondrocyte zones in fetal mouse tibias treated with CNP [13].
  • In the CNS, gene transcripts for CNP were present at the onset of neurogenesis, embryonic day 10.5 (E10.5), primarily in the dorsal part of the ventricular zone (VZ) throughout the hindbrain and spinal cord [14].
  • Moreover, CNP, alone and in combination with sonic hedgehog (Shh), induced the expression of the Shh target gene gli-1 in hindbrain cultures, suggesting that natriuretic peptides may also modify patterning events in the embryonic brain [14].
  • CNP also exhibited modest survival-promoting effects for sensory neurons [14].

Associations of Nppc with chemical compounds

  • C-type natriuretic peptide (CNP), a third member of the natriuretic peptide family, occurs at the growth plate and acts locally as a positive regulator of endochondral ossification through the intracellular accumulation of cyclic GMP (cGMP) [3].
  • Conversely, upon high glucose, the CNP-induced production of cGMP was elevated twofold in stretched and in control cells [15].
  • In GC-A -/- hearts, the immediate contractile responses to CNP and 8-pCPT-cGMP were significantly enhanced [16].
  • (3) The potency of ANP and CNP in aortae from WT animals was increased in the presence of the NOS inhibitor, N(G)-nitro-L-arginine (3 x 10(-4) M) and the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolol[4,3,a]quinoxalin-1-one (5 x 10(-6) M) [17].
  • Both CNP and 8-bromo cGMP dose-dependently decreased [3H]thymidine uptake, without affecting alkaline phosphatase activity [18].

Physical interactions of Nppc

  • GC-B2 binds CNP, but the ligand fails to activate the cyclase, while GC-B3 fails to bind ligand [19].

Regulatory relationships of Nppc

  • In contrast, CNP induced concentration-dependent vasorelaxations of GC-A -/- and SMC GC-A KO RRA [12].
  • We conclude that CNP is synthesized in the pituitary, where it is located predominantly in gonadotropes, and GC-B receptors expressed in the pituitary mediate the direct effects of CNP in gonadotropes [20].
  • These results provide the first demonstration that CNP has a negative chronotropic effect on heart rate and suggest that this effect is mediated by selectively activating NPR-C and reducing ICa(L) through coupling to Gi protein [21].

Other interactions of Nppc

  • This study suggests the physiologic significance of the CNP/GC-B pathway in the process of endochondral ossification [13].
  • CNP increased the cGMP production much more potently than ANP, thereby resulting in an increase in the total longitudinal bone length [13].
  • This study provides in vivo and in vitro genetic evidence that cGKII plays a critical role in CNP-mediated endochondral ossification [3].
  • Induction of Nppc occurred in identical cell populations to those in which Wnt4 is induced after renal injury [2].
  • Such changes in CNP responsiveness did not affect large arteries as the aorta and they were not due to vascular changes secondary to chronic arterial hypertension in GC-A -/- mice [12].

Analytical, diagnostic and therapeutic context of Nppc

  • RT-PCR showed that podocytes express mRNA not only for NPR-B but also for CNP [15].
  • Immunohistochemistry revealed CNP-positive cells in the anterior, but not posterior, pituitaries of rats, and the vast majority of these cells were identified as gonadotropes by colocalization of CNP and LH immunoreactivities [20].
  • Its specific guanylyl cyclase-containing receptor, GC-B, is also expressed on several anterior pituitary cell types, and CNP potently stimulates cGMP accumulation in rat pituitary cell cultures and pituitary cell lines [22].
  • The messages for GC-A and GC-B were demonstrated by means of Northern blot analysis, and the presence of CNP was shown by Southern blotting coupled with reverse transcription-polymerase chain reaction (RT-PCR) [23].
  • Cell numbers were determined by counting, and real-time PCR was performed to examine regulation of genes in the CNP signaling pathway by DEX [24].


  1. Dwarfism and early death in mice lacking C-type natriuretic peptide. Chusho, H., Tamura, N., Ogawa, Y., Yasoda, A., Suda, M., Miyazawa, T., Nakamura, K., Nakao, K., Kurihara, T., Komatsu, Y., Itoh, H., Tanaka, K., Saito, Y., Katsuki, M., Nakao, K. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  2. CNP gene expression is activated by Wnt signaling and correlates with Wnt4 expression during renal injury. Surendran, K., Simon, T.C. Am. J. Physiol. Renal Physiol. (2003) [Pubmed]
  3. Cyclic GMP-dependent protein kinase II plays a critical role in C-type natriuretic peptide-mediated endochondral ossification. Miyazawa, T., Ogawa, Y., Chusho, H., Yasoda, A., Tamura, N., Komatsu, Y., Pfeifer, A., Hofmann, F., Nakao, K. Endocrinology (2002) [Pubmed]
  4. Isolation, mapping, and regulated expression of the gene encoding mouse C-type natriuretic peptide. Huang, H., Acuff, C.G., Steinhelper, M.E. Am. J. Physiol. (1996) [Pubmed]
  5. Renal C-type natriuretic peptide and natriuretic peptide receptor B mRNA expression are affected by water deprivation in the Spinifex Hopping mouse. Heimeier, R.A., Donald, J.A. Comp. Biochem. Physiol., Part A Mol. Integr. Physiol. (2003) [Pubmed]
  6. Analgesic and behavioral effects of a 100 microT specific pulsed extremely low frequency magnetic field on control and morphine treated CF-1 mice. Shupak, N.M., Hensel, J.M., Cross-Mellor, S.K., Kavaliers, M., Prato, F.S., Thomas, A.W. Neurosci. Lett. (2004) [Pubmed]
  7. Overexpression of CNP in chondrocytes rescues achondroplasia through a MAPK-dependent pathway. Yasoda, A., Komatsu, Y., Chusho, H., Miyazawa, T., Ozasa, A., Miura, M., Kurihara, T., Rogi, T., Tanaka, S., Suda, M., Tamura, N., Ogawa, Y., Nakao, K. Nat. Med. (2004) [Pubmed]
  8. Expression and differential regulation of natriuretic peptides in mouse macrophages. Vollmar, A.M., Schulz, R. J. Clin. Invest. (1995) [Pubmed]
  9. Functional effects of C-type natriuretic peptide and nitric oxide are attenuated in hypertrophic myocytes from pressure-overloaded mouse hearts. Su, J., Zhang, Q., Moalem, J., Tse, J., Scholz, P.M., Weiss, H.R. Am. J. Physiol. Heart Circ. Physiol. (2005) [Pubmed]
  10. A monoclonal antibody raised to corpus callosum extract reacts with 2',3'-cyclic nucleotide 3'-phosphohydrolase. Brenner, T., Lisak, R.P., Rostami, A., McMorris, F.A., Silberberg, D.H. J. Neurochem. (1986) [Pubmed]
  11. C-type natriuretic peptide attenuates bleomycin-induced pulmonary fibrosis in mice. Murakami, S., Nagaya, N., Itoh, T., Fujii, T., Iwase, T., Hamada, K., Kimura, H., Kangawa, K. Am. J. Physiol. Lung Cell Mol. Physiol. (2004) [Pubmed]
  12. Diverging vasorelaxing effects of C-type natriuretic peptide in renal resistance arteries and aortas of GC-A-deficient mice. Steinmetz, M., Potthast, R., Sabrane, K., Kuhn, M. Regul. Pept. (2004) [Pubmed]
  13. Natriuretic peptide regulation of endochondral ossification. Evidence for possible roles of the C-type natriuretic peptide/guanylyl cyclase-B pathway. Yasoda, A., Ogawa, Y., Suda, M., Tamura, N., Mori, K., Sakuma, Y., Chusho, H., Shiota, K., Tanaka, K., Nakao, K. J. Biol. Chem. (1998) [Pubmed]
  14. Embryonic expression and multifunctional actions of the natriuretic peptides and receptors in the developing nervous system. DiCicco-Bloom, E., Lelièvre, V., Zhou, X., Rodriguez, W., Tam, J., Waschek, J.A. Dev. Biol. (2004) [Pubmed]
  15. C-type natriuretic peptide as a podocyte hormone and modulation of its cGMP production by glucose and mechanical stress. Lewko, B., Endlich, N., Kriz, W., Stepinski, J., Endlich, K. Kidney Int. (2004) [Pubmed]
  16. Increased effects of C-type natriuretic peptide on cardiac ventricular contractility and relaxation in guanylyl cyclase A-deficient mice. Pierkes, M., Gambaryan, S., Bokník, P., Lohmann, S.M., Schmitz, W., Potthast, R., Holtwick, R., Kuhn, M. Cardiovasc. Res. (2002) [Pubmed]
  17. Vascular natriuretic peptide receptor-linked particulate guanylate cyclases are modulated by nitric oxide-cyclic GMP signalling. Madhani, M., Scotland, R.S., MacAllister, R.J., Hobbs, A.J. Br. J. Pharmacol. (2003) [Pubmed]
  18. C-type natriuretic peptide as an autocrine/paracrine regulator of osteoblast. Evidence for possible presence of bone natriuretic peptide system. Suda, M., Tanaka, K., Fukushima, M., Natsui, K., Yasoda, A., Komatsu, Y., Ogawa, Y., Itoh, H., Nakao, K. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  19. Regulation of the guanylyl cyclase-B receptor by alternative splicing. Tamura, N., Garbers, D.L. J. Biol. Chem. (2003) [Pubmed]
  20. C-type natriuretic peptide (CNP) in the pituitary: is CNP an autocrine regulator of gonadotropes? McArdle, C.A., Olcese, J., Schmidt, C., Poch, A., Kratzmeier, M., Middendorff, R. Endocrinology (1994) [Pubmed]
  21. Effects of C-type natriuretic peptide on ionic currents in mouse sinoatrial node: a role for the NPR-C receptor. Rose, R.A., Lomax, A.E., Kondo, C.S., Anand-Srivastava, M.B., Giles, W.R. Am. J. Physiol. Heart Circ. Physiol. (2004) [Pubmed]
  22. C-type natriuretic peptide (CNP) effects in anterior pituitary cell lines: evidence for homologous desensitisation of CNP-stimulated cGMP accumulation in alpha T3-1 gonadotroph-derived cells. Fowkes, R.C., Forrest-Owen, W., McArdle, C.A. J. Endocrinol. (2000) [Pubmed]
  23. C-type natriuretic peptide/guanylate cyclase B system in ATDC5 cells, a chondrogenic cell line. Suda, M., Tanaka, K., Yasoda, A., Komatsu, Y., Chusho, H., Miura, M., Tamura, N., Ogawa, Y., Nakao, K. J. Bone Miner. Metab. (2002) [Pubmed]
  24. Dexamethasone stimulates expression of C-type Natriuretic Peptide in chondrocytes. Agoston, H., Baybayan, L., Beier, F. BMC musculoskeletal disorders (2006) [Pubmed]
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