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Gene Review

IHH  -  indian hedgehog

Homo sapiens

Synonyms: BDA1, HHG-2, HHG2, Indian hedgehog protein
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Disease relevance of IHH


High impact information on IHH

  • PTHrP delays the hypertrophic differentiation of proliferating chondrocytes, whereas IHH promotes chondrocyte proliferation [5].
  • In diffuse cancers, IHH was expressed in cells with an epithelial phenotype and SHH in cells with a mesenchymal phenotype [6].
  • This study examined whether SHH, 2 other ligands IHH and Desert hedgehog, and receptors or downstream targets are expressed in normal gastric epithelium or in intestinal and diffuse-type gastric cancers [6].
  • Homozygous mutations in IHH cause acrocapitofemoral dysplasia, an autosomal recessive disorder with cone-shaped epiphyses in hands and hips [7].
  • Using a candidate-gene approach, we identified two missense mutations in the amino-terminal signaling domain of the gene encoding Indian hedgehog (IHH) [7].

Chemical compound and disease context of IHH


Biological context of IHH

  • Furthermore, we show that cells within the bone-perichondrial ring in controls and patients express IHH, PTHR1, and type 10 and type 1 collagen transcripts, suggesting that bone-perichondrial ring formation involves cells of both chondrocytic and osteoblastic phenotypes [9].
  • PTHR1 and IHH expression in growth plates, bone-perichondrial rings and vascular canals is not affected by FGFR3 mutations, irrespective of the mutant genotype and age, and is in keeping with cell phenotypes [9].
  • Examination of single nucleotide polymorphisms (SNP) has shown that the affected individuals in both families share SNPs within IHH consistent with that of a common founder [10].
  • Inhibition of hedgehog signaling in TAKA-1 pancreatic ductal cells using cyclopamine significantly reduced their growth through cell cycle arrest, while stimulation of the IHH pathway enhanced the growth of these cells [11].
  • IHH plays a role in pancreas organogenesis and differentiation, as well as in the regulation of insulin production [11].

Anatomical context of IHH


Associations of IHH with chemical compounds


Other interactions of IHH

  • Indian Hedgehog (IHH), together with parathyroid hormone-like hormone (PTHLH), participates in the organization of growth plates in long bones [1].
  • The family of HH proteins consists of at least three different members, i.e., sonic HH (SHH), Indian HH (IHH), and desert HH (DHH) [16].
  • Correlation between diabetic and non-diabetic CP patients revealed no significant difference in IHH, SMO, or PTC immunoreactivity [11].
  • Indian hedgehog (IHH) and its receptors patched (PTC) and smoothened (SMO) belong to the hedgehog family of signaling molecules, which are essential for a variety of patterning events during mammalian tIssue development [11].
  • The polarized features allowed the use of IHH cells for the study of localization of the newly characterized multidrug resistance protein MRP1 [15].

Analytical, diagnostic and therapeutic context of IHH


  1. Peripheral chondrosarcoma progression is accompanied by decreased Indian Hedgehog signalling. Hameetman, L., Rozeman, L.B., Lombaerts, M., Oosting, J., Taminiau, A.H., Cleton-Jansen, A.M., Bovée, J.V., Hogendoorn, P.C. J. Pathol. (2006) [Pubmed]
  2. Constitutive hedgehog signaling in chondrosarcoma up-regulates tumor cell proliferation. Tiet, T.D., Hopyan, S., Nadesan, P., Gokgoz, N., Poon, R., Lin, A.C., Yan, T., Andrulis, I.L., Alman, B.A., Wunder, J.S. Am. J. Pathol. (2006) [Pubmed]
  3. Absence of IHH and retention of PTHrP signalling in enchondromas and central chondrosarcomas. Rozeman, L.B., Hameetman, L., Cleton-Jansen, A.M., Taminiau, A.H., Hogendoorn, P.C., Bovée, J.V. J. Pathol. (2005) [Pubmed]
  4. Is there a role for the IHH gene in Hirschsprung's disease? Garcia-Barceló, M.M., Lee, W.S., Sham, M.H., Lui, V.C., Tam, P.K. Neurogastroenterol. Motil. (2003) [Pubmed]
  5. A mutant PTH/PTHrP type I receptor in enchondromatosis. Hopyan, S., Gokgoz, N., Poon, R., Gensure, R.C., Yu, C., Cole, W.G., Bell, R.S., Jüppner, H., Andrulis, I.L., Wunder, J.S., Alman, B.A. Nat. Genet. (2002) [Pubmed]
  6. Hedgehog signal activation in gastric pit cell and in diffuse-type gastric cancer. Fukaya, M., Isohata, N., Ohta, H., Aoyagi, K., Ochiya, T., Saeki, N., Yanagihara, K., Nakanishi, Y., Taniguchi, H., Sakamoto, H., Shimoda, T., Nimura, Y., Yoshida, T., Sasaki, H. Gastroenterology (2006) [Pubmed]
  7. Homozygous mutations in IHH cause acrocapitofemoral dysplasia, an autosomal recessive disorder with cone-shaped epiphyses in hands and hips. Hellemans, J., Coucke, P.J., Giedion, A., De Paepe, A., Kramer, P., Beemer, F., Mortier, G.R. Am. J. Hum. Genet. (2003) [Pubmed]
  8. Defective chondrocyte proliferation and differentiation in osteochondromas of MHE patients. Benoist-Lasselin, C., de Margerie, E., Gibbs, L., Cormier, S., Silve, C., Nicolas, G., LeMerrer, M., Mallet, J.F., Munnich, A., Bonaventure, J., Zylberberg, L., Legeai-Mallet, L. Bone (2006) [Pubmed]
  9. Parathyroid hormone receptor type 1/Indian hedgehog expression is preserved in the growth plate of human fetuses affected with fibroblast growth factor receptor type 3 activating mutations. Cormier, S., Delezoide, A.L., Benoist-Lasselin, C., Legeai-Mallet, L., Bonaventure, J., Silve, C. Am. J. Pathol. (2002) [Pubmed]
  10. A novel mutation in the IHH gene causes brachydactyly type A1: a 95-year-old mystery resolved. McCready, M.E., Sweeney, E., Fryer, A.E., Donnai, D., Baig, A., Racacho, L., Warman, M.L., Hunter, A.G., Bulman, D.E. Hum. Genet. (2002) [Pubmed]
  11. Distribution of Indian hedgehog and its receptors patched and smoothened in human chronic pancreatitis. Kayed, H., Kleeff, J., Keleg, S., Büchler, M.W., Friess, H. J. Endocrinol. (2003) [Pubmed]
  12. Hedgehog signaling pathway and gastrointestinal stem cell signaling network (Review). Katoh, Y., Katoh, M. Int. J. Mol. Med. (2006) [Pubmed]
  13. Indian hedgehog and beta-catenin signaling: role in the sebaceous lineage of normal and neoplastic mammalian epidermis. Niemann, C., Unden, A.B., Lyle, S., Zouboulis, C.h.C., Toftgård, R., Watt, F.M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  14. Cloning, expression, and chromosomal location of SHH and IHH: two human homologues of the Drosophila segment polarity gene hedgehog. Marigo, V., Roberts, D.J., Lee, S.M., Tsukurov, O., Levi, T., Gastier, J.M., Epstein, D.J., Gilbert, D.J., Copeland, N.G., Seidman, C.E. Genomics (1995) [Pubmed]
  15. Immortalized human hepatocytes as a tool for the study of hepatocytic (de-)differentiation. Schippers, I.J., Moshage, H., Roelofsen, H., Müller, M., Heymans, H.S., Ruiters, M., Kuipers, F. Cell Biol. Toxicol. (1997) [Pubmed]
  16. Clinical aspects of disrupted Hedgehog signaling (Review). Oldak, M., Grzela, T., Lazarczyk, M., Malejczyk, J., Skopinski, P. Int. J. Mol. Med. (2001) [Pubmed]
  17. EXT-related pathways are not involved in the pathogenesis of dysplasia epiphysealis hemimelica and metachondromatosis. Bovée, J.V., Hameetman, L., Kroon, H.M., Aigner, T., Hogendoorn, P.C. J. Pathol. (2006) [Pubmed]
  18. Assignment of Indian hedgehog (IHH) to human chromosome bands 2q33-->q35 by in situ hybridization. Leek, J.P., Moynihan, T.P., Anwar, R., Bonthron, D.T., Markham, A.F., Lench, N.J. Cytogenet. Cell Genet. (1997) [Pubmed]
  19. Differentiation of normal male prepuberty and hypogonadotrophic hypogonadism using an ultrasensitive luteinizing hormone assay. Brown, D.C., Stirling, H.F., Butler, G.E., Kelnar, C.J., Wu, F.C. Horm. Res. (1996) [Pubmed]
  20. Isolated hypoxic hepatic perfusion with orthograde or retrograde flow in patients with irresectable liver metastases using percutaneous balloon catheter techniques: a phase I and II study. van Etten, B., Brunstein, F., van IJken, M.G., Marinelli, A.W., Verhoef, C., van der Sijp, J.R., Guetens, G., de Boeck, G., de Bruijn, E.A., de Wilt, J.H., Eggermont, A.M. Ann. Surg. Oncol. (2004) [Pubmed]
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