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Gene Review

GRHL3  -  grainyhead-like 3 (Drosophila)

Homo sapiens

Synonyms: Grainyhead-like protein 3 homolog, SOM, Sister of mammalian grainyhead, TFCP2L4, Transcription factor CP2-like 4, ...
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Disease relevance of GRHL3

  • The study is a preliminary single-blind, placebo- and prednisolone-controlled investigation of the treatment of 156 children with otitis media with effusion (secretory otitis media, SOM), ranging from 2 to 12 years [1].
  • Temporal bones from patients with OM were classified as cases of acute purulent (POM), serous (SOM), mucoid or secretory (MOM), or chronic otitis media (COM) [2].
  • Granuloma macrophages produce SOM [3].
  • OBJECTIVE: The purpose of our study was to compare vacuum-assisted suction drainage (VASD) to conventional wound management, in the treatment of poststernotomy osteomyelitis (SOM) [4].
  • Previous human pharmacological and toxicological studies demonstrated advantages of the combination drug Somnium [SOM, lorazepam (LOR) 1 mg plus diphenhydramine 25 mg] over 1 mg LOR alone, as it showed synergistic effects in hypnotic properties and antagonistic effects in regard to toxicity [5].

Psychiatry related information on GRHL3

  • In the present double-blind, parallel-group study, hypnotic and anxiolytic effects of SOM were studied in 44 patients with non-organic insomnia related to mild generalized anxiety disorder (GAD), as compared with LOR alone [5].
  • Noopsychic performance remained improved in both groups, with a superiority of SOM to LOR in regard to reaction time and reaction time variability [5].
  • Descriptive statistics demonstrated further a significant improvement of sleep efficiency and total sleep time after SOM and of wakefulness time and number of awakenings during the total sleep period after both drugs, but no interdrug differences [5].
  • In psychophysiology, critical flicker frequency decreased more under SOM than LOR [5].
  • In a double-blind, parallel-group design study on hypnotic and anxiolytic effects of the combination drug Somnium (lorazepam 1 mg + diphenhydramine 25 mg) (SOM) as compared with 1 mg lorazepam (LOR) alone, daytime behavioral effects were studied in 44 patients with nonorganic insomnia related to a mild generalized anxiety disorder [6].

High impact information on GRHL3

  • To understand the mechanisms underlying the synergistic/additive action of these agents, we applied cDNA microarrays, component plane presentation integrated self-organizing map (CPP-SOM), and methods of protein biochemistry to study cell apoptosis induced by imatinib mesylate, ATO, and the combination of the 2 agents in the CML cell line K562 [7].
  • The area under the plasma and urinary xylose curves was lowered by somatostatin only on day SOM [8].
  • When the blood glucose rose above 4.1 mmol/l, an external artificial pancreas was used to infuse either extra insulin (day INS) or somatostatin for either 3h (day som) or the entire 8h experimental period (day SOM) [8].
  • Like grainyhead, the SOM gene too produces several distinct isoforms with differing functional properties through alternative splicing [9].
  • The application of the SOM network in drug design and molecular diversity is discussed [10].

Chemical compound and disease context of GRHL3


Biological context of GRHL3

  • Using gene targeting in mice, we have shown that Grhl3 is essential for neural tube closure, skin barrier formation and wound healing [11].
  • These findings expand our understanding of the unique role of Grhl3 in neurulation and epidermal morphogenesis, and provide a focus for further functional analysis of the Grhl genes during mouse embryogenesis [11].
  • Despite their extensive sequence homology, Grhl1 and Grhl2 are unable to compensate for loss of Grhl3 in these developmental processes [11].
  • The non-grid technique for modeling 3D QSAR using self-organizing neural network (SOM) and PLS analysis: application to steroids and colchicinoids [12].
  • Previously mathematical techniques, such as computing the receptive field (using electrophysiology data) and artificial neural networks (Kohonen network or SOM and back propagation network) have been used to decode neural signals [13].

Anatomical context of GRHL3

  • The lamina propria has an extensive network of nerves using the neuropeptides SOM, SP, and VIP [14].
  • SOM, SP, and VIP can act as potent regulators of lymphoid cell proliferation and interleukin and immunoglobulin production [14].
  • In an effort to find novel complex I inhibitors which exhibited anticancer activity in the NCI's tumor cell line screen, we examined organized tumor cytotoxicity screening data available as SOM (self-organized maps) () at the developmental therapeutics program (DTP) of the National Cancer Institute (NCI) [15].
  • We further found that SOM by itself markedly affected the secretion of proinflammatory cytokines from intestinal epithelial cells, which play a major role in the gut immunity in the mucosal defense against invading microorganisms [16].
  • One of the identified genes is the transcription factor Grhl3, which we found to be expressed in the superficial layer of the gastrula ectoderm and the neurula epidermis [17].

Associations of GRHL3 with chemical compounds

  • The effectiveness of hydroxyzine is discussed in the context of the pathophysiology of SOM, especially with respect to mast cells and their activation by allergic and nonallergic means [1].
  • Porcine peptide with N-terminal tyrosine and C-terminal tyrosine (PYY), GIP, SOM and hpGRF-40 were inactive [18].
  • We studied the effect of VIP, SOM, S-P and Bomb on thymidine incorporation into human colonic lamina propria lymphocyte (LPL) DNA [19].
  • Average pyrene absorption efficiency (AE(pyr): -65%) varied inversely with SOM quality and IR(pyr) [20].
  • Histamine concentrations were significantly higher than plasma levels for SOM fluid and nasopharyngeal secretion [21].

Analytical, diagnostic and therapeutic context of GRHL3

  • The biliary-type classification allows a clinician to stratify patients who would benefit from SOM and endoscopic sphincterotomy [22].
  • The topographic localization of neurons containing SOM mRNA in the human brain is in agreement with previous studies using immunocytochemical or radioimmunoassay techniques [23].
  • These results show that in situ hybridization histochemistry with oligonucleotide probes can be used to map the distribution of neurons expressing SOM mRNA in human postmortem materials [23].
  • Gas chromatography mass spectrometry (GC/ MS) of lipid extracts of SOM fractions provided data for PAH distribution histograms, compound weathering ratios, and alkylated and nonalkylated PAH concentrations [24].
  • The innervation of Rana ridibunda esophagus myenteric plexuses has been studied by the following methods: demonstration of cholinesterase activity; FIF method for catecholamines; immunohistochemistry for VIP, SP and SOM, and conventional electron microscopy [25].


  1. Treatment of secretory otitis media with local instillation of hydroxyzine. Theoharides, T.C., Manolidis, S.S., Vliagoftis, H., Manolidis, L.S. Int. Arch. Allergy Immunol. (1994) [Pubmed]
  2. Subepithelial space in otitis media. Paparella, M.M., Sipilä, P., Juhn, S.K., Jung, T.T. Laryngoscope (1985) [Pubmed]
  3. The substance P and somatostatin interferon-gamma immunoregulatory circuit. Weinstock, J.V., Elliott, D. Ann. N. Y. Acad. Sci. (1998) [Pubmed]
  4. Vacuum-assisted suction drainage versus conventional treatment in the management of poststernotomy osteomyelitis. Doss, M., Martens, S., Wood, J.P., Wolff, J.D., Baier, C., Moritz, A. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. (2002) [Pubmed]
  5. Nonorganic insomnia in generalized anxiety disorder. 2. Comparative studies on sleep, awakening, daytime vigilance and anxiety under lorazepam plus diphenhydramine (Somnium) versus lorazepam alone, utilizing clinical, polysomnographic and EEG mapping methods. Saletu, B., Saletu-Zyhlarz, G., Anderer, P., Brandstätter, N., Frey, R., Gruber, G., Klösch, G., Mandl, M., Grünberger, J., Linzmayer, L. Neuropsychobiology (1997) [Pubmed]
  6. Comparative studies on the effects of the combination drug lorazepam plus diphenhydramine (Somnium) versus lorazepam on the noopsyche, thymopsyche and psychophysiology in nonorganic insomnia related to generalized anxiety disorder. Grünberger, J., Saletu, B., Linzmayer, L., Böck, G., Weissgram, S., Brandstaätter, N., Frey, R., Saletu-Zyhlarz, G. Methods and findings in experimental and clinical pharmacology. (1997) [Pubmed]
  7. Coordination of intrinsic, extrinsic, and endoplasmic reticulum-mediated apoptosis by imatinib mesylate combined with arsenic trioxide in chronic myeloid leukemia. Du, Y., Wang, K., Fang, H., Li, J., Xiao, D., Zheng, P., Chen, Y., Fan, H., Pan, X., Zhao, C., Zhang, Q., Imbeaud, S., Graudens, E., Eveno, E., Auffray, C., Chen, S., Chen, Z., Zhang, J. Blood (2006) [Pubmed]
  8. Effects of somatostatin added to insulin in a glucose-controlled insulin infusion system. Selam, J.L., Chenon, D., Pham, T.C., Gagnol, J.P., Sany, C., Thomas, N., Gravagne, G., Orsetti, A., Mirouze, J. Diabetologia (1981) [Pubmed]
  9. The identification and characterization of human Sister-of-Mammalian Grainyhead (SOM) expands the grainyhead-like family of developmental transcription factors. Ting, S.B., Wilanowski, T., Cerruti, L., Zhao, L.L., Cunningham, J.M., Jane, S.M. Biochem. J. (2003) [Pubmed]
  10. Comparative molecular surface analysis: a novel tool for drug design and molecular diversity studies. Polanski, J., Gieleciak, R. Mol. Divers. (2003) [Pubmed]
  11. Spatial and temporal expression of the Grainyhead-like transcription factor family during murine development. Auden, A., Caddy, J., Wilanowski, T., Ting, S.B., Cunningham, J.M., Jane, S.M. Gene Expr. Patterns (2006) [Pubmed]
  12. The non-grid technique for modeling 3D QSAR using self-organizing neural network (SOM) and PLS analysis: application to steroids and colchicinoids. Polański, J. SAR and QSAR in environmental research. (2000) [Pubmed]
  13. Decoding of auditory cortex signals with a LAMSTAR neural network. Muralidharan, A., Rousche, P.J. Neurol. Res. (2005) [Pubmed]
  14. Neuroimmunomodulation in the intestinal mucosa. Ottaway, C.A. Gastroenterol. Clin. North Am. (1991) [Pubmed]
  15. Data mining of NCI's anticancer screening database reveals mitochondrial complex I inhibitors cytotoxic to leukemia cell lines. Glover, C.J., Rabow, A.A., Isgor, Y.G., Shoemaker, R.H., Covell, D.G. Biochem. Pharmacol. (2007) [Pubmed]
  16. Nerve-driven immunity: neuropeptides regulate cytokine secretion of T cells and intestinal epithelial cells in a direct, powerful and contextual manner. Levite, M., Chowers, Y. Ann. Oncol. (2001) [Pubmed]
  17. Grainyhead-like 3, a transcription factor identified in a microarray screen, promotes the specification of the superficial layer of the embryonic epidermis. Chalmers, A.D., Lachani, K., Shin, Y., Sherwood, V., Cho, K.W., Papalopulu, N. Mech. Dev. (2006) [Pubmed]
  18. Secretin receptor activity in rat gastric glands. Binding studies, cAMP generation and pharmacology. Gespach, C., Bataille, D., Vauclin, N., Moroder, L., Wünsch, E., Rosselin, G. Peptides (1986) [Pubmed]
  19. Gastrointestinal neuropeptides suppress human colonic lamina propria lymphocyte DNA synthesis. Elitsur, Y., Luk, G.D. Peptides (1990) [Pubmed]
  20. Role of sediment organic matter quality and feeding history in dietary absorption and accumulation of pyrene in the mud snail (Hydrobia ulvae). Granberg, M.E., Forbes, T.L. Environ. Toxicol. Chem. (2006) [Pubmed]
  21. Mast cells and histamine in adenoid tissue and middle ear. Palva, T., Taskinen, E., Lehtinen, T., Ramsay, H., Björksten, F., Hackman, P. Acta Otolaryngol. (1991) [Pubmed]
  22. Sphincter of Oddi dysfunction and other functional biliary disorders: evaluation and treatment. Prajapati, D.N., Hogan, W.J. Gastroenterol. Clin. North Am. (2003) [Pubmed]
  23. Regional distribution of neuropeptide somatostatin gene expression in the human brain. Mengod, G., Rigo, M., Savasta, M., Probst, A., Palacios, J.M. Synapse (1992) [Pubmed]
  24. Impact of vegetation on sedimentary organic matter composition and polycyclic aromatic hydrocarbon attenuation. Gregory, S.T., Shea, D., Guthrie-Nichols, E. Environ. Sci. Technol. (2005) [Pubmed]
  25. Intrinsic and extrinsic innervation of the amphibians esophagic myenteric plexuses. Junquera, C., Azanza, M.J., Parra, P., Peg, M.T., Aisa, J., Romero, L.M., Garín, P. Histol. Histopathol. (1988) [Pubmed]
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