Consequences of the loss of the Grainyhead-like 1 gene for renal gene expression, regulation of blood pressure and heart rate in a mouse model
Languages of publication
Aim: The Grainyhead-like 1 (GRHL1) transcription factor is tissue-specific and is very highly expressed in the kidney. In humans the GRHL1 gene is located at the chromosomal position 2p25. A locus conferring increased susceptibility to essential hypertension has been mapped to 2p25 in two independent studies, but the causative gene has never been identified. Furthermore, a statistically significant association has been found between a polymorphism in the GRHL1 gene and heart rate regulation. The aim of our study was to investigate the physiological consequences of Grhl1 loss in a mouse model and ascertain whether Grhl1 may be involved in the regulation of blood pressure and heart rate. Experimental approach: In our research we employed the Grhl1 "knock-out" mouse strain. We analyzed renal gene expression, blood pressure and heart rate in the Grhl1-null mice in comparison with their "wild-type" littermate controls. Most important results: The expression of many genes is altered in the Grhl1-/- kidneys. Some of these genes have previously been linked to blood pressure regulation. Despite this, the Grhl1-null mice have normal blood pressure and interestingly, increased heart rate. Conclusions: Our work did not discover any new evidence to suggest any involvement of Grhl1 in blood pressure regulation. However, we determined that the loss of Grhl1 influences the regulation of heart rate in a mouse model.
- Andres-Hernando A, Lanaspa MA, Rivard CJ, Berl T (2008) Nucleoporin 88 (Nup88) is regulated by hypertonic stress in kidney cells to retain the transcription factor tonicity enhancer-binding protein (TonEBP) in the nucleus. J Biol Chem 283: 25082-25090.
- Angius A, Petretto E, Maestrale GB, Forabosco P, Casu G, Piras D, Fanciulli M, Falchi M, Melis PM, Palermo M, Pirastu M (2002) A new essential hypertension susceptibility locus on chromosome 2p24-p25, detected by genomewide search. Am J Hum Genet 71: 893-905.
- Arikan AA, Citak A (2008) Pediatric shock. Signa Vitae 3: 13-23.
- Auden A, Caddy J, Wilanowski T, Ting SB, Cunningham JM, Jane SM (2006) Spatial and temporal expression of the Grainyhead-like transcription factor family during murine development. Gene Expr Patterns 6: 964-970.
- Benjamini Y, Hochberg Y (1995) Controlling the False Discovery Rate - a Practical and Powerful Approach to Multiple Testing. J Roy Stat Soc B Met 57: 289-300.
- Caddy J, Wilanowski T, Darido C, Dworkin S, Ting SB, Zhao Q, Rank G, Auden A, Srivastava S, Papenfuss TA, Murdoch JN, Humbert PO, Boulos N, Weber T, Zuo J, Cunningham JM, Jane SM (2010) Epidermal wound repair is regulated by the planar cell polarity signaling pathway. Dev Cell 19: 138-147.
- Carvalho BS, Irizarry RA (2010) A framework for oligonucleotide microarray preprocessing. Bioinformatics 26: 2363-2367.
- Chaignon M, Bellet M, Lucsko M, Rapoud C, Guedon J (1986) Acute and chronic effects of a new calcium inhibitor, nicardipine, on renal hemodynamics in hypertension. J Cardiovascular Pharmacol 8: 892-897.
- Currie G, Freel EM, Perry CG, Dominiczak AF (2012) Disorders of blood pressure regulation-role of catecholamine biosynthesis, release, and metabolism. Curr Hypertens Reports 14: 38-45.
- Darido C, Georgy SR, Wilanowski T, Dworkin S, Auden A, Zhao Q, Rank G, Srivastava S, Finlay MJ, Papenfuss AT, Pandolfi PP, Pearson RB, Jane SM (2011) Targeting of the tumor suppressor GRHL3 by a miR-21-dependent proto-oncogenic network results in PTEN Loss and Tumorigenesis. Cancer Cell 20: 635-648.
- Dynlacht BD, Attardi LD, Admon A, Freeman M, Tjian R (1989) Functional analysis of NTF-1, a developmentally regulated Drosophila transcription factor that binds neuronal cis elements. Genes Dev 3: 1677-1688.
- Edgar R, Domrachev M, Lash AE (2002) Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res 30: 207-210.
- Fabian J, Lodrini M, Oehme I, Schier MC, Thole TM, Hielscher T, Kopp-Schneider A, Opitz L, Capper D, von Deimling A, Wiegand I, Milde T, Mahlknecht U, Westermann F, Popanda O, Roels F, Hero B, Berthold F, Fischer M, Kulozik AE, Witt O, Deubzer HE (2014) GRHL1 Acts as tumor suppressor in neuroblastoma and is negatively regulated by MYCN and HDAC3. Cancer Res 74: 2604-2616.
- Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J, Hornik K, Hothorn T, Huber W, Iacus S, Irizarry R, Leisch F, Li C, Maechler M, Rossini AJ, Sawitzki G, Smith C, Smyth G, Tierney L, Yang JY, Zhang J (2004) Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5: R80.
- Harris RC, Zhang MZ (2012) Dopamine, the kidney, and hypertension. Curr Hypertension Reports 14: 138-143.
- He R, Geha RS (2010) Thymic stromal lymphopoietin. Ann N Y Acad Sci 1183: 13-24.
- Hsin YH, Tang CH, Lai HT, Lee TH (2011) The role of TonEBP in regulation of AAD expression and dopamine production in renal proximal tubule cells upon hypertonic challenge. Biochem Biophys Res Commun 414: 598-603.
- Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, Speed TP (2003) Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 4: 249-264.
- Juarez MT, Patterson RA, Sandoval-Guillen E, McGinnis W (2011) Duox, Flotillin-2, and Src42A are required to activate or delimit the spread of the transcriptional response to epidermal wounds in Drosophila. PLoS Genetics 7: e1002424.
- Kamide K, Kokubo Y, Yang J, Tanaka C, Hanada H, Takiuchi S, Inamoto N, Banno M, Kawano Y, Okayama A, Tomoike H, Miyata T (2005) Hypertension susceptibility genes on chromosome 2p24-p25 in a general Japanese population. J Hypertens 23: 955-960.
- Kamide K, Yang J, Matayoshi T, Takiuchi S, Horio T, Yoshii M, Miwa Y, Yasuda H, Yoshihara F, Nakamura S, Nakahama H, Miyata T, Kawano Y (2009) Genetic polymorphisms of L-type calcium channel alpha1C and alpha1D subunit genes are associated with sensitivity to the antihypertensive effects of L-type dihydropyridine calcium-channel blockers. Circulation Journal: Official Jurnal of the Japanese Circulation Society 73: 732-740.
- Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM, Haussler D (2002) The human genome browser at UCSC. Genome Res 12: 996-1006.
- Koutnikova H, Laakso M, Lu L, Combe R, Paananen J, Kuulasmaa T, Kuusisto J, Haring HU, Hansen T, Pedersen O, Smith U, Hanefeld M, Williams RW, Auwerx J (2009) Identification of the UBP1 locus as a critical blood pressure determinant using a combination of mouse and human genetics. PLoS Genetics 5: e1000591.
- Malkoff J (2005) Non-invasive blood pressure for mice and rats. Animal Lab News, Kent Scientific Corporation Nov/Dec: 1-12.
- Messerli FH, Williams B, Ritz E (2007) Essential hypertension. Lancet 370: 591-603.
- Mlacki M, Darido C, Jane SM, Wilanowski T (2014) Loss of Grainy head-like 1 is associated with disruption of the epidermal barrier and squamous cell carcinoma of the skin. PloS One 9: e89247.
- Neumar RW, Otto CW, Link MS, Kronick SL, Shuster M, Callaway CW, Kudenchuk PJ, Ornato JP, McNally B, Silvers SM, Passman RS, White RD, Hess EP, Tang W, Davis D, Sinz E, Morrison LJ (2010) Part 8: Adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 122: S729-767.
- Pare A, Kim M, Juarez MT, Brody S, McGinnis W (2012) The functions of grainy head-like proteins in animals and fungi and the evolution of apical extracellular barriers. PloS One 7: e36254.
- Pravenec M, Kazdova L, Landa V, Zidek V, Mlejnek P, Simakova M, Jansa P, Forejt J, Kren V, Krenova D, Qi N, Wang JM, Chan D, Aitman TJ, Kurtz TW (2008) Identification of mutated Srebf1 as a QTL influencing risk for hepatic steatosis in the spontaneously hypertensive rat. Hypertension 51: 148-153.
- Rankinen T, Sung YJ, Sarzynski MA, Rice TK, Rao DC, Bouchard C (2012) Heritability of submaximal exercise heart rate response to exercise training is accounted for by nine SNPs. J Appl Physiol 112: 892-897.
- Singh P, Bahrami L, Castillo A, Majid DS (2013) TNF-alpha type 2 receptor mediates renal inflammatory response to chronic angiotensin II administration with high salt intake in mice. Am J Physiol Renal Physiol 304: F991-999.
- Smyth GK, Michaud J, Scott HS (2005) Use of within-array replicate spots for assessing differential expression in microarray experiments. Bioinformatics 21: 2067-2075.
- Wang X, Seed B (2003) A PCR primer bank for quantitative gene expression analysis. Nucleic Acids Res 31: e154.
- Wilanowski T, Caddy J, Ting SB, Hislop NR, Cerruti L, Auden A, Zhao LL, Asquith S, Ellis S, Sinclair R, Cunningham JM, Jane SM (2008) Perturbed desmosomal cadherin expression in grainy head-like 1-null mice. Embo J 27: 886-897.
- Wilanowski T, Tuckfield A, Cerruti L, O'Connell S, Saint R, Parekh V, Tao J, Cunningham JM, Jane SM (2002) A highly conserved novel family of mammalian developmental transcription factors related to Drosophila grainyhead. Mech Dev 114: 37-50.
- Wu M, Yang C, Tao B, Bu S, Guay-Woodford LM (2013) The ciliary protein cystin forms a regulatory complex with necdin to modulate Myc expression. PloS One 8: e83062.
- Yamaguchi Y, Yonemura S, Takada S (2006) Grainyhead-related transcription factor is required for duct maturation in the salivary gland and the kidney of the mouse. Development 133: 4737-4748.
- Yu P, Yang Z, Jones JE, Wang Z, Owens SA, Mueller SC, Felder RA, Jose PA (2004) D1 dopamine receptor signaling involves caveolin-2 in HEK-293 cells. Kidney Int 66: 2167-2180.
- Zhang MZ, Yao B, Wang S, Fan X, Wu G, Yang H, Yin H, Yang S, Harris RC (2011) Intrarenal dopamine deficiency leads to hypertension and decreased longevity in mice. J Clin Invest 121: 2845-2854.
- Zhou Y, Luo P, Chang HH, Huang H, Yang T, Dong Z, Wang CY, Wang MH (2008) Colfibrate attenuates blood pressure and sodium retention in DOCA-salt hypertension. Kidney Int 74: 1040-1048.
- Zhu DL, Wang HY, Xiong MM, He X, Chu SL, Jin L, Wang GL, Yuan WT, Zhao GS, Boerwinkle E, Huang W (2001) Linkage of hypertension to chromosome 2q14-q23 in Chinese families. J Hypertens 19: 55-61.
Publication order reference