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Article: Néphrocytes et podocytes, même combat?

Umbhauer, Muriel

2009 Volume 25, Issue 1, Page(s) 27

Title translation	Nephrocytes and podocytes, even fight?.
MeSH term(s)	Animals ; Drosophila/anatomy & histology ; Drosophila/cytology ; Insecta/anatomy & histology ; Malpighian Tubules/anatomy & histology ; Malpighian Tubules/cytology ; Malpighian Tubules/physiology ; Podocytes/cytology ; Podocytes/physiology
Language	French
Publishing date	2009-01
Publishing country	France
Document type	News
ZDB-ID	632733-3
ISSN	1958-5381 ; 0767-0974
ISSN (online)	1958-5381
ISSN	0767-0974
DOI	10.1051/medsci/200925127
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Article ; Online: Retinoic acid control of pax8 during renal specification of Xenopus pronephros involves hox and meis3.

Durant-Vesga, Jennifer / Suzuki, Nanoka / Ochi, Haruki / Le Bouffant, Ronan / Eschstruth, Alexis / Ogino, Hajime / Umbhauer, Muriel / Riou, Jean-François

Developmental biology

2022 Volume 493, Page(s) 17–28

Abstract: Development of the Xenopus pronephros relies on renal precursors grouped at neurula stage into a specific region of dorso-lateral mesoderm called the kidney field. Formation of the kidney field at early neurula stage is dependent on retinoic (RA) ... ...

Abstract	Development of the Xenopus pronephros relies on renal precursors grouped at neurula stage into a specific region of dorso-lateral mesoderm called the kidney field. Formation of the kidney field at early neurula stage is dependent on retinoic (RA) signaling acting upstream of renal master transcriptional regulators such as pax8 or lhx1. Although lhx1 might be a direct target of RA-mediated transcriptional activation in the kidney field, how RA controls the emergence of the kidney field remains poorly understood. In order to better understand RA control of renal specification of the kidney field, we have performed a transcriptomic profiling of genes affected by RA disruption in lateral mesoderm explants isolated prior to the emergence of the kidney field and cultured at different time points until early neurula stage. Besides genes directly involved in pronephric development (pax8, lhx1, osr2, mecom), hox (hoxa1, a3, b3, b4, c5 and d1) and the hox co-factor meis3 appear as a prominent group of genes encoding transcription factors (TFs) downstream of RA. Supporting the idea of a role of meis3 in the kidney field, we have observed that meis3 depletion results in a severe inhibition of pax8 expression in the kidney field. Meis3 depletion only marginally affects expression of lhx1 and aldh1a2 suggesting that meis3 principally acts upstream of pax8. Further arguing for a role of meis3 and hox in the control of pax8, expression of a combination of meis3, hoxb4 and pbx1 in animal caps induces pax8 expression, but not that of lhx1. The same combination of TFs is also able to transactivate a previously identified pax8 enhancer, Pax8-CNS1. Mutagenesis of potential PBX-Hox binding motifs present in Pax8-CNS1 further allows to identify two of them that are necessary for transactivation. Finally, we have tested deletions of regulatory sequences in reporter assays with a previously characterized transgene encompassing 36.5 kb of the X. tropicalis pax8 gene that allows expression of a truncated pax8-GFP fusion protein recapitulating endogenous pax8 expression. This transgene includes three conserved pax8 enhancers, Pax8-CNS1, Pax8-CNS2 and Pax8-CNS3. Deletion of Pax8-CNS1 alone does not affect reporter expression, but deletion of a 3.5 kb region encompassing Pax8-CNS1 and Pax8-CNS2 results in a severe inhibition of reporter expression both in the otic placode and kidney field domains.
MeSH term(s)	Animals ; Xenopus laevis/genetics ; Xenopus laevis/metabolism ; Tretinoin/pharmacology ; Tretinoin/metabolism ; Xenopus Proteins/genetics ; Xenopus Proteins/metabolism ; Paired Box Transcription Factors/genetics ; Paired Box Transcription Factors/metabolism ; Gene Expression Regulation, Developmental ; Pronephros/metabolism ; Kidney/metabolism ; Aldehyde Dehydrogenase 1 Family ; Retinal Dehydrogenase/metabolism
Chemical Substances	Tretinoin (5688UTC01R) ; Xenopus Proteins ; Paired Box Transcription Factors ; aldh1a2 protein, Xenopus (EC 1.2.1.36) ; Aldehyde Dehydrogenase 1 Family (EC 1.2.1) ; Retinal Dehydrogenase (EC 1.2.1.36)
Language	English
Publishing date	2022-10-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1114-9
ISSN	1095-564X ; 0012-1606
ISSN (online)	1095-564X
ISSN	0012-1606
DOI	10.1016/j.ydbio.2022.10.009
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Article ; Online: Characterization of potential TRPP2 regulating proteins in early Xenopus embryos.

Futel, Mélinée / Le Bouffant, Ronan / Buisson, Isabelle / Umbhauer, Muriel / Riou, Jean-François

Journal of cellular biochemistry

2018 Volume 119, Issue 12, Page(s) 10338–10350

Abstract: Transient receptor potential cation channel-2 (TRPP2) is a nonspecific ... ...

Abstract	Transient receptor potential cation channel-2 (TRPP2) is a nonspecific Ca
MeSH term(s)	Animals ; Calcium/metabolism ; Cilia/genetics ; Dishevelled Proteins/genetics ; Endoplasmic Reticulum/genetics ; Epithelial Cells/metabolism ; Gastrula/embryology ; Gastrula/metabolism ; Gene Expression Regulation, Developmental ; Kidney/embryology ; Kidney/metabolism ; Signal Transduction/genetics ; TRPP Cation Channels/genetics ; Xenopus Proteins/genetics ; Xenopus laevis/embryology ; Xenopus laevis/genetics
Chemical Substances	Dishevelled Proteins ; Dvl2 protein, Xenopus ; TRPP Cation Channels ; Xenopus Proteins ; polycystic kidney disease 2 protein ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2018-09-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	392402-6
ISSN	1097-4644 ; 0730-2312
ISSN (online)	1097-4644
ISSN	0730-2312
DOI	10.1002/jcb.27376
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Article ; Online: Hnf1b haploinsufficiency differentially affects developmental target genes in a new renal cysts and diabetes mouse model.

Niborski, Leticia L / Paces-Fessy, Mélanie / Ricci, Pierbruno / Bourgeois, Adeline / Magalhães, Pedro / Kuzma-Kuzniarska, Maria / Lesaulnier, Celine / Reczko, Martin / Declercq, Edwige / Zürbig, Petra / Doucet, Alain / Umbhauer, Muriel / Cereghini, Silvia

Disease models & mechanisms

2021 Volume 14, Issue 5

Abstract: Heterozygous mutations in HNF1B cause the complex syndrome renal cysts and diabetes (RCAD), characterized by developmental abnormalities of the kidneys, genital tracts and pancreas, and a variety of renal, pancreas and liver dysfunctions. The ... ...

Abstract	Heterozygous mutations in HNF1B cause the complex syndrome renal cysts and diabetes (RCAD), characterized by developmental abnormalities of the kidneys, genital tracts and pancreas, and a variety of renal, pancreas and liver dysfunctions. The pathogenesis underlying this syndrome remains unclear as mice with heterozygous null mutations have no phenotype, while constitutive/conditional Hnf1b ablation leads to more severe phenotypes. We generated a novel mouse model carrying an identified human mutation at the intron-2 splice donor site. Unlike heterozygous mice previously characterized, mice heterozygous for the splicing mutation exhibited decreased HNF1B protein levels and bilateral renal cysts from embryonic day 15, originated from glomeruli, early proximal tubules (PTs) and intermediate nephron segments, concurrently with delayed PT differentiation, hydronephrosis and rare genital tract anomalies. Consistently, mRNA sequencing showed that most downregulated genes in embryonic kidneys were primarily expressed in early PTs and the loop of Henle and involved in ion/drug transport, organic acid and lipid metabolic processes, while the expression of previously identified targets upon Hnf1b ablation, including cystic disease genes, was weakly or not affected. Postnatal analyses revealed renal abnormalities, ranging from glomerular cysts to hydronephrosis and, rarely, multicystic dysplasia. Urinary proteomics uncovered a particular profile predictive of progressive decline in kidney function and fibrosis, and displayed common features with a recently reported urine proteome in an RCAD pediatric cohort. Altogether, our results show that reduced HNF1B levels lead to developmental disease phenotypes associated with the deregulation of a subset of HNF1B targets. They further suggest that this model represents a unique clinical/pathological viable model of the RCAD disease.
MeSH term(s)	Animals ; Animals, Newborn ; Cell Polarity ; Central Nervous System Diseases/genetics ; Central Nervous System Diseases/pathology ; Cilia/pathology ; Dental Enamel/abnormalities ; Dental Enamel/pathology ; Diabetes Mellitus, Experimental/genetics ; Diabetes Mellitus, Experimental/pathology ; Diabetes Mellitus, Type 2/genetics ; Diabetes Mellitus, Type 2/pathology ; Disease Models, Animal ; Embryo, Mammalian/pathology ; Gene Dosage ; Gene Expression Profiling ; Genes, Developmental ; Haploinsufficiency/genetics ; Hepatocyte Nuclear Factor 1-beta/genetics ; Heterozygote ; Humans ; Hydronephrosis/complications ; Kidney Diseases, Cystic/genetics ; Kidney Diseases, Cystic/pathology ; Kidney Glomerulus/pathology ; Kidney Tubules/pathology ; Mice, Inbred C57BL ; Mutation/genetics ; Nephrons/pathology ; RNA Splicing/genetics ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Severity of Illness Index ; Mice
Chemical Substances	HNF1B protein, human ; Hnf1b protein, mouse ; RNA, Messenger ; Hepatocyte Nuclear Factor 1-beta (138674-15-4)
Language	English
Publishing date	2021-05-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2451104-3
ISSN	1754-8411 ; 1754-8403
ISSN (online)	1754-8411
ISSN	1754-8403
DOI	10.1242/dmm.047498
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Article ; Online: Pou3f transcription factor expression during embryonic development highlights distinct pou3f3 and pou3f4 localization in the Xenopus laevis kidney.

Cosse-Etchepare, Camille / Gervi, Isabelle / Buisson, Isabelle / Formery, Laurent / Schubert, Michael / Riou, Jean-François / Umbhauer, Muriel / Le Bouffant, Ronan

The International journal of developmental biology

2018 Volume 62, Issue 4-5, Page(s) 325–333

Abstract: The POU (Pit-Oct-Unc) genes encode a large transcription factor family comprising 6 classes (pou1f to pou6f ) involved in many developmental processes, such as cell commitment and differentiation. The pou3f class contains four members (pou3f1, pou3f2, ... ...

Abstract	The POU (Pit-Oct-Unc) genes encode a large transcription factor family comprising 6 classes (pou1f to pou6f ) involved in many developmental processes, such as cell commitment and differentiation. The pou3f class contains four members (pou3f1, pou3f2, pou3f3, pou3f4) characterized by expression in ectodermal tissue derivatives, such as nervous system and otic vesicle, during mammalian development. In order to obtain insights into the potential conservation of this class of transcription factors in vertebrates, we carried out a phylogenetic analysis and a comprehensive comparative study of pou3f expression in the frog Xenopus laevis. All vertebrates examined possessed members of the four pou3f subfamilies, excepting the zebrafish, which lacked a pou3f4 gene. Whole mount in situ hybridization and real-time quantitative polymerase chain reaction (RT-qPCR) analyses revealed that Xenopus pou3f genes were expressed in the forming neural tube and their expression was maintained in the brain, mostly in the dorsal part, at tailbud stages. The pou3f2, pou3f3, and pou3f4 genes were also expressed in the developing otic vesicle, and pou3f1 in some cells of the epidermis. Besides ectodermal derivatives, pou3f3 and pou3f4 were expressed in the developing kidney. Their expression started at the early tailbud stage in the pronephric anlage and partly overlapped. In the mature pronephric tubule, pou3f3 was restricted to the intermediate tubule, while pou3f4 was also expressed in the distal and connecting tubule. Together, our results highlight a significant conservation of pou3f gene expression in vertebrates and indicate that they may have distinct but also redundant functions during neural and renal development.
MeSH term(s)	Animals ; Brain/embryology ; Brain/metabolism ; Embryo, Nonmammalian/metabolism ; Embryonic Development/physiology ; Gene Expression Regulation, Developmental ; Kidney/embryology ; Kidney/metabolism ; Organogenesis/physiology ; POU Domain Factors/genetics ; POU Domain Factors/metabolism ; Xenopus Proteins/genetics ; Xenopus Proteins/metabolism ; Xenopus laevis/embryology
Chemical Substances	POU Domain Factors ; Xenopus Proteins
Language	English
Publishing date	2018-06-06
Publishing country	Spain
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1036070-0
ISSN	1696-3547 ; 0214-6282
ISSN (online)	1696-3547
ISSN	0214-6282
DOI	10.1387/ijdb.170260RL
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Article ; Online: Pax8 and Pax2 are specifically required at different steps of Xenopus pronephros development.

Buisson, Isabelle / Le Bouffant, Ronan / Futel, Mélinée / Riou, Jean-François / Umbhauer, Muriel

Developmental biology

2015 Volume 397, Issue 2, Page(s) 175–190

Abstract: The respective role of Pax2 and Pax8 in early kidney development in vertebrates is poorly understood. In this report, we have studied the roles of Pax8 and Pax2 in Xenopus pronephros development using a loss-of-function approach. Our results highlight a ... ...

Abstract	The respective role of Pax2 and Pax8 in early kidney development in vertebrates is poorly understood. In this report, we have studied the roles of Pax8 and Pax2 in Xenopus pronephros development using a loss-of-function approach. Our results highlight a differential requirement of these two transcription factors for proper pronephros formation. Pax8 is necessary for the earliest steps of pronephric development and its depletion leads to a complete absence of pronephric tubule. Pax2 is required after the establishment of the tubule pronephric anlage, for the expression of several terminal differentiation markers of the pronephric tubule. Neither Pax2 nor Pax8 is essential to glomus development. We further show that Pax8 controls hnf1b, but not lhx1 and Osr2, expression in the kidney field as soon as the mid-neurula stage. Pax8 is also required for cell proliferation of pronephric precursors in the kidney field. It may exert its action through the wnt/beta-catenin pathway since activation of this pathway can rescue MoPax8 induced proliferation defect and Pax8 regulates expression of the wnt pathway components, dvl1 and sfrp3. Finally, we observed that loss of pronephros in Pax8 morphants correlates with an expanded vascular/blood gene expression domain indicating that Pax8 function is important to delimit the blood/endothelial genes expression domain in the anterior part of the dorso-lateral plate.
MeSH term(s)	Animals ; Bromodeoxyuridine ; DNA Primers/genetics ; Gene Expression Regulation, Developmental/genetics ; In Situ Hybridization ; PAX2 Transcription Factor/metabolism ; PAX8 Transcription Factor ; Paired Box Transcription Factors/metabolism ; Polymerase Chain Reaction ; Pronephros/embryology ; Real-Time Polymerase Chain Reaction ; Wnt Signaling Pathway/genetics ; Wnt Signaling Pathway/physiology ; Xenopus/embryology ; Xenopus/genetics ; Xenopus Proteins/metabolism
Chemical Substances	DNA Primers ; PAX2 Transcription Factor ; PAX8 Transcription Factor ; Paired Box Transcription Factors ; Pax8 protein, Xenopus ; Xenopus Proteins ; Bromodeoxyuridine (G34N38R2N1)
Language	English
Publishing date	2015-01-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1114-9
ISSN	1095-564X ; 0012-1606
ISSN (online)	1095-564X
ISSN	0012-1606
DOI	10.1016/j.ydbio.2014.10.022
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Article ; Online: Differential expression of arid5b isoforms in Xenopus laevis pronephros.

Le Bouffant, Ronan / Cunin, Anne-Claire / Buisson, Isabelle / Cartry, Jérôme / Riou, Jean-François / Umbhauer, Muriel

The International journal of developmental biology

2014 Volume 58, Issue 5, Page(s) 363–368

Abstract: Arid5b belongs to the ARID family of transcription factors characterised by a helix-turn-helix motif- based DNA-binding domain called ARID (A-T Rich Interaction Domain). In human, alternative splicing leads to long and short isoforms (isoform1 and 2, ... ...

Abstract	Arid5b belongs to the ARID family of transcription factors characterised by a helix-turn-helix motif- based DNA-binding domain called ARID (A-T Rich Interaction Domain). In human, alternative splicing leads to long and short isoforms (isoform1 and 2, respectively) which differ in their N-terminal part. In this study, we report the cloning and expression pattern of Xenopus laevis arid5b. We have isolated a full length cDNA that shows homology with the human arid5b isoform1. Furthermore, 5'RACE experiments revealed the presence of a shorter isoform equivalent to the human isoform2. Temporal expression analysis by RT-qPCR indicated that X. laevis arid5b isoform1 and isoform2 are differentially expressed during development. Isoform1 is strongly expressed maternally, while isoform2 expression is essentially restricted to tailbud stages. Spatial expression analysis by whole mount in situ showed that arid5b is predominantly expressed in the developing pronephros. Arid5b mRNAs are detected in the antero-dorsal part of the pronephros anlage at the early tailbud stage and later on, in the proximal part of the pronephric tubule. RT-qPCR analyses with primers that allow to discriminate isoform1 from isoform2 showed that the latter is enriched in the pronephros anlage. In agreement with a specific pronephric signature of the isoform2, we also observed that isoform2 but not isoform1 is upregulated in animal caps induced to form pronephric tissue in response to activin A and retinoic acid. These results indicate that the two arid5b isoforms are differentially expressed and likely play different roles during early Xenopus development.
MeSH term(s)	Animals ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Embryo, Nonmammalian/metabolism ; Gene Expression Regulation, Developmental ; Pronephros/embryology ; Pronephros/metabolism ; Protein Isoforms/genetics ; Protein Isoforms/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Xenopus Proteins/genetics ; Xenopus Proteins/metabolism ; Xenopus laevis
Chemical Substances	DNA-Binding Proteins ; Protein Isoforms ; Transcription Factors ; Xenopus Proteins
Language	English
Publishing date	2014
Publishing country	Spain
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1036070-0
ISSN	1696-3547 ; 0214-6282
ISSN (online)	1696-3547
ISSN	0214-6282
DOI	10.1387/ijdb.140029mu
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Article ; Online: TRPP2-dependent Ca2+ signaling in dorso-lateral mesoderm is required for kidney field establishment in Xenopus.

Futel, Mélinée / Leclerc, Catherine / Le Bouffant, Ronan / Buisson, Isabelle / Néant, Isabelle / Umbhauer, Muriel / Moreau, Marc / Riou, Jean-François

Journal of cell science

2015 Volume 128, Issue 5, Page(s) 888–899

Abstract: In Xenopus laevis embryos, kidney field specification is dependent on retinoic acid (RA) and coincides with a dramatic increase of Ca(2+) transients, but the role of Ca(2+) signaling in the kidney field is unknown. Here, we identify TRPP2, a member of ... ...

Abstract	In Xenopus laevis embryos, kidney field specification is dependent on retinoic acid (RA) and coincides with a dramatic increase of Ca(2+) transients, but the role of Ca(2+) signaling in the kidney field is unknown. Here, we identify TRPP2, a member of the transient receptor potential (TRP) superfamily of channel proteins encoded by the pkd2 gene, as a central component of Ca(2+) signaling in the kidney field. TRPP2 is strongly expressed at the plasma membrane where it might regulate extracellular Ca(2+) entry. Knockdown of pkd2 in the kidney field results in the downregulation of pax8, but not of other kidney field genes (lhx1, osr1 and osr2). We further show that inhibition of Ca(2+) signaling with an inducible Ca(2+) chelator also causes downregulation of pax8, and that pkd2 knockdown results in a severe inhibition of Ca(2+) transients in kidney field explants. Finally, we show that disruption of RA results both in an inhibition of intracellular Ca(2+) signaling and of TRPP2 incorporation into the plasma membrane of kidney field cells. We propose that TRPP2-dependent Ca(2+) signaling is a key component of pax8 regulation in the kidney field downstream of RA-mediated non-transcriptional control of TRPP2.
MeSH term(s)	Animals ; Calcium Signaling/physiology ; Embryo, Nonmammalian/cytology ; Embryo, Nonmammalian/embryology ; Kidney/cytology ; Kidney/embryology ; PAX8 Transcription Factor ; Paired Box Transcription Factors/genetics ; Paired Box Transcription Factors/metabolism ; TRPP Cation Channels/genetics ; TRPP Cation Channels/metabolism ; Xenopus Proteins/genetics ; Xenopus Proteins/metabolism ; Xenopus laevis
Chemical Substances	PAX8 Transcription Factor ; Paired Box Transcription Factors ; Pax8 protein, Xenopus ; TRPP Cation Channels ; Xenopus Proteins
Language	English
Publishing date	2015-03-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2993-2
ISSN	1477-9137 ; 0021-9533
ISSN (online)	1477-9137
ISSN	0021-9533
DOI	10.1242/jcs.155499
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Article ; Online: Retinoic acid-dependent control of MAP kinase phosphatase-3 is necessary for early kidney development in Xenopus.

Le Bouffant, Ronan / Wang, Jian-Hong / Futel, Mélinée / Buisson, Isabelle / Umbhauer, Muriel / Riou, Jean-François

Biology of the cell

2012 Volume 104, Issue 9, Page(s) 516–532

Abstract: Background information: In Xenopus, the functional kidney of the tadpole, the pronephros, forms from the kidney field, which is specified at completion of gastrulation. Specification of the kidney field requires retinoic acid (RA) signalling during ... ...

Abstract	Background information: In Xenopus, the functional kidney of the tadpole, the pronephros, forms from the kidney field, which is specified at completion of gastrulation. Specification of the kidney field requires retinoic acid (RA) signalling during gastrulation, while fibroblast growth factor (FGF) signals inhibit should be inhibit this process. Results: We have analysed the functional interactions taking place during gastrulation between RA and FGF signals in the lateral marginal zone (LMZ), that is in the environment of unspecified pronephric mesoderm precursors. Inhibition of FGF receptor (FGFR) signalling with SU5402 does not significantly affect expression of genes encoding RA metabolism enzymes and RA receptor-α in LMZ explants. Furthermore, SU5402 has no effect on the expression of hoxa1, a major RA target in the LMZ, showing that FGF is not antagonising RA in the LMZ. Disruption of RA signalling affects FGF ligand production to some extent, especially FGF8b, but the strongest effect is the down-regulation of the mitogen-activated protein kinase phosphatase-3 (MKP3)-encoding gene, mkp3. A strong up-regulation of mkp3 occurs in response to exogenous RA. This effect is reduced in a context of FGFR inhibition, suggesting that RA and FGF signals are co-operating upstream of mkp3. Mkp3 knockdown results in an inhibition of the kidney field markers pax8 and lhx1 and in a defective development of the pronephros. Conclusions: FGF is not negatively influencing pronephric specification by antagonising RA signalling. Functional interactions between RA and FGF rather take place at the level of the transcriptional regulation of mkp3, indicating that RA may antagonise FGF signalling at the level of the extracellular signal-regulated kinase (Erk) pathway. A fine tuning of Erk signalling by MKP3 is important for the proper establishment of the kidney field.
MeSH term(s)	Animals ; Dual Specificity Phosphatase 6 ; Female ; Fibroblast Growth Factors/metabolism ; Gene Expression Regulation, Developmental ; Kidney/embryology ; Kidney/enzymology ; Kidney/metabolism ; Male ; Phosphoprotein Phosphatases/genetics ; Phosphoprotein Phosphatases/metabolism ; Receptors, Fibroblast Growth Factor/genetics ; Receptors, Fibroblast Growth Factor/metabolism ; Signal Transduction ; Tretinoin/metabolism ; Xenopus Proteins/genetics ; Xenopus Proteins/metabolism ; Xenopus laevis/embryology ; Xenopus laevis/genetics ; Xenopus laevis/metabolism
Chemical Substances	Receptors, Fibroblast Growth Factor ; Xenopus Proteins ; Tretinoin (5688UTC01R) ; Fibroblast Growth Factors (62031-54-3) ; Phosphoprotein Phosphatases (EC 3.1.3.16) ; DUSP6 protein, Xenopus (EC 3.1.3.48) ; Dual Specificity Phosphatase 6 (EC 3.1.3.48)
Language	English
Publishing date	2012-06-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	245745-3
ISSN	1768-322X ; 0399-0311 ; 0248-4900
ISSN (online)	1768-322X
ISSN	0399-0311 ; 0248-4900
DOI	10.1111/boc.201200005
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Article ; Online: Urinary proteome signature of Renal Cysts and Diabetes syndrome in children.

Ricci, Pierbruno / Magalhães, Pedro / Krochmal, Magdalena / Pejchinovski, Martin / Daina, Erica / Caruso, Maria Rosa / Goea, Laura / Belczacka, Iwona / Remuzzi, Giuseppe / Umbhauer, Muriel / Drube, Jens / Pape, Lars / Mischak, Harald / Decramer, Stéphane / Schaefer, Franz / Schanstra, Joost P / Cereghini, Silvia / Zürbig, Petra

Scientific reports

2019 Volume 9, Issue 1, Page(s) 2225

Abstract: Renal Cysts and Diabetes Syndrome (RCAD) is an autosomal dominant disorder caused by mutations in the HNF1B gene encoding for the transcriptional factor hepatocyte nuclear factor-1B. RCAD is characterized as a multi-organ disease, with a broad spectrum ... ...

Abstract	Renal Cysts and Diabetes Syndrome (RCAD) is an autosomal dominant disorder caused by mutations in the HNF1B gene encoding for the transcriptional factor hepatocyte nuclear factor-1B. RCAD is characterized as a multi-organ disease, with a broad spectrum of symptoms including kidney abnormalities (renal cysts, renal hypodysplasia, single kidney, horseshoe kidneys, hydronephrosis), early-onset diabetes mellitus, abnormal liver function, pancreatic hypoplasia and genital tract malformations. In the present study, using capillary electrophoresis coupled to mass spectrometry (CE-MS), we investigated the urinary proteome of a pediatric cohort of RCAD patients and different controls to identify peptide biomarkers and obtain further insights into the pathophysiology of this disorder. As a result, 146 peptides were found to be associated with RCAD in 22 pediatric patients when compared to 22 healthy age-matched controls. A classifier based on these peptides was generated and further tested on an independent cohort, clearly discriminating RCAD patients from different groups of controls. This study demonstrates that the urinary proteome of pediatric RCAD patients differs from autosomal dominant polycystic kidney disease (PKD1, PKD2), congenital nephrotic syndrome (NPHS1, NPHS2, NPHS4, NPHS9) as well as from chronic kidney disease conditions, suggesting differences between the pathophysiology behind these disorders.
MeSH term(s)	Adolescent ; Biomarkers/urine ; Central Nervous System Diseases/diagnosis ; Central Nervous System Diseases/metabolism ; Central Nervous System Diseases/urine ; Child ; Child, Preschool ; Dental Enamel/abnormalities ; Dental Enamel/metabolism ; Diabetes Mellitus, Type 2/diagnosis ; Diabetes Mellitus, Type 2/metabolism ; Diabetes Mellitus, Type 2/urine ; Diagnosis, Differential ; Female ; Humans ; Kidney Diseases, Cystic/diagnosis ; Kidney Diseases, Cystic/metabolism ; Kidney Diseases, Cystic/urine ; Male ; Mass Spectrometry ; Peptides/urine ; Phenotype ; Proteome ; Proteomics/methods ; Reproducibility of Results
Chemical Substances	Biomarkers ; Peptides ; Proteome
Language	English
Publishing date	2019-02-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-38713-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

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