Allele-Specific Expression at the<i>RET</i>Locus in Blood and Gut Tissue of Individuals Carrying Risk Alleles for Hirschsprung Disease

Matera, Ivana; Musso, Marco; Griseri, Paola; Rusmini, Marta; Duca, Marco Di; So, Man Ting; Mavilio, Domenico; Miao, Xiaoping; Tam, Peter; Ravazzolo, Roberto; Ceccherini, Isabella; Garcia-Barceló, Mercè

doi:10.1002/humu.22302

Cited by 4 publications

(5 citation statements)

References 25 publications

(42 reference statements)

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“…Moreover, we found that RET expression in cells either treated or not with GDNF does not correlate with any particular RET genotype, including the SNP tagging the predisposing RET haplotype (SNP2). The absence of undescribed variants lying in putative regulatory regions has also confirmed recent findings which suggest different tissue and time specific regulations of RET in adult and embryo (Matera et al, ). Similar negative results were also obtained when we attempted to draw a correlation between RET expression and gender.…”

Section: Discussionsupporting

confidence: 78%

“…As shown in Figure , RET shows different mRNA levels in the PBMCs of two unrelated healthy donors (namely PBMC1 and PBMC2), a finding consistent with the amount of RET receptors we detected, as already reported (Rusmini et al, ), on the surface of the same PBMCs (data not shown). Previous observations regarding the high variability of RET receptor expressed on immune circulating cells are therefore confirmed (Matera et al, ; Rusmini et al, ). In addition, we also failed to explain the variable RET expression, as assessed by measuring mRNA and protein levels, in terms of both sex and age differences among donors' PBMCs (data not shown).…”

Section: Resultssupporting

confidence: 58%

“…RET expression was also investigated in circulating immune cells and it has been reported to be present on monocytes, polymorphonucleated, B and CD34 + stem cells (Visser et al, ; Gattei et al, ), although RET phenotypic distribution on peripheral blood mononuclear cells has been controversial for many years (Vargas‐Leal et al, ; Veiga‐Fernandes et al, ). Only recently, two studies conducted both in healthy individuals and in HSCR patients characterized the RET expression in PBMCs (Matera et al, ; Rusmini et al, ).…”

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confidence: 99%

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Expression Variability and Function of the RET Gene in Adult Peripheral Blood Mononuclear Cells

Rusmini

Griseri

Matera

et al. 2014

Journal Cellular Physiology

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RET is a gene playing a key role during embryogenesis and in particular during the enteric nervous system development. High levels of RET gene expression are maintained in different human tissues also in adulthood, although their physiological role remains unclear. In particular, collected evidences of a RET contribution in the development and maintenance of the immune system prompted us to investigate its levels of surface expression on peripheral blood mononuclear cells (PBMCs) from adult healthy donors. Despite variability among samples, RET expression was conserved at similar levels in the different immune cell subsets, with higher correlations in similar lymphocyte populations (i.e. CD4(+) and CD8(+) T cells). Conversely, no correlation was found between the amount of RET receptor, the expression of its putative ligands and co-receptors and the genotypes at the RET locus. Moreover, we investigated the RET-associated inflammatory pathways in PBMCs from healthy donors both in resting conditions and upon glial cell derived neurotrophic factor (GDNF) and GPI-linked co-receptors alpha 1 (GFRα1) mediated RET activation. RET mRNA levels positively correlated with the transcript amount of interleukin-8 (IL-8), a cytokine produced by monocytes and macrophages, though we could not demonstrate its direct effect on RET expression by in vitro experiments on THP1 human monocytic cells. These results imply that RET expression might be influenced by either cis- and/or trans-factors, which together would account for its high variability within the general population, and suggest a putative functional role of the RET gene in modulating immune cell responses during inflammation and carcinogenesis.

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Section: Discussionsupporting

confidence: 78%

Section: Resultssupporting

confidence: 58%

mentioning

confidence: 99%

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Expression Variability and Function of the RET Gene in Adult Peripheral Blood Mononuclear Cells

Rusmini

Griseri

Matera

et al. 2014

Journal Cellular Physiology

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“…Single-nucleotide primer extension was performed using a specific kit (SNaPshot Multiplex Sistem, Thermo Fisher ® ) and oligos suitable for the mutation site (p.R79C) on both strand (forward primer: 5′-GAGATGATGGAGCTCAATGACC-3; reverse primer: 5′-CTTCTCGATGTAGCTGGCAAAG-3′), followed by capillary electrophoresis on automated DNA sequencer (ABI PRISM ® 3130XL), according to a protocol already reported ( Matera et al, 2013 ).…”

Section: Methodsmentioning

confidence: 99%

“…The PCR product of exon 1 was cloned using the genomic DNA of ID#110M subject as a template, into the TOPO TA vector (Invitrogen, Carlsbad, CA, USA) following the manufacturer’s instructions. The plasmid DNA isolated from 51 clones was directly sequenced using the Sanger protocol, as already reported ( Matera et al, 2013 ).…”

Section: Methodsmentioning

confidence: 99%

Parental Somatic Mosaicism Uncovers Inheritance of an Apparently De Novo GFAP Mutation

et al. 2021

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Alexander disease is a leukodystrophy caused by heterozygous mutations of GFAP gene. Recurrence in siblings from healthy parents provides a confirmation to the transmission of variants through germinal mosaicism. With the use of DNA isolated from peripheral blood, next-generation sequencing (NGS) of GFAP locus was performed with deep coverage (≥500×) in 11 probands and their parents (trios) with probands heterozygous for apparently de novo GFAP mutations. Indeed, one parent had somatic mosaicism, estimated in the range of 8.9%–16%, for the mutant allele transmitted to the affected sibling. Parental germline mosaicism deserves attention, as it is critical in assessing the risk of recurrence in families with Alexander disease.

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TGF-β1, Ghrelin, Neurexin, and Neuroligin are Predictive Biomarkers for Postoperative Prognosis of Laparoscopic Surgery in Children with Hirschsprung Disease

Xiao

Zhu

Yang

et al. 2014

Cell Biochem Biophys

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The study was set to analyze the predictive values of transforming growth factor β1 (TGF-β1), Ghrelin, Neurexin, and Neuroligin protein expression on postoperative prognosis of laparoscopic surgery in children with Hirschsprung disease. 281 cases of children with Hirschsprung disease, admitted into Guangdong Women and Children Hospital and Guangzhou women and children's medical center from March 2009 to March 2014, were treated with laparoscopic radical surgery for Hirschsprung disease. They were divided into the good and the poor prognosis groups according to their recuperation and complications. Protein expressions of TGF-β1, Ghrelin, Neurexin, and Neuroligin were prospectively analyzed. The correlations between the expressions of these proteins and the prognosis were analyzed. There were 129 cases of children with poor prognosis, accounting for 45.9 %. There were no significant differences in the expressions of TGF-β1 mRNA and proteins within the group in both the groups (p > 0.05). TGF-β1 mRNA and protein expressions of the poor prognosis group were significantly higher than those of the good prognosis group in each segment of intestine (p < 0.05). Protein detection results manifested that Ghrelin protein expression gradually increased along narrow segment, transitional segment, and expansion segment in both groups. Ghrelin protein expression of the poor prognosis group was significantly lower than that of the good prognosis group in each segment of intestine (p < 0.05). There were significant differences in the protein expressions of Neurexin and Neuroligin within the group. The protein expressions of Neurexin and Neuroligin in expansion segment were the highest. Neurexin and Neuroligin protein expressions of the poor prognosis group were significantly lower than those of the good prognosis group in each segment of intestine (p < 0.05). Increasing expression of TGF-β1 protein, decreasing expressions of Ghrelin, Neurexin, and Neuroligin proteins can induce the loss or dysfunction of ganglion cells in distal intestinal canal, which is closely correlated with the occurrences of adverse prognosis, such as increased intestinal peristalsis recovery time, increased complication rate etc., in children. It has a high value for predicting prognosis of children patients with Hirschsprung disease after surgical intervention.

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Allele-Specific Expression at theRETLocus in Blood and Gut Tissue of Individuals Carrying Risk Alleles for Hirschsprung Disease

Cited by 4 publications

References 25 publications

Expression Variability and Function of the RET Gene in Adult Peripheral Blood Mononuclear Cells

Expression Variability and Function of the RET Gene in Adult Peripheral Blood Mononuclear Cells

Parental Somatic Mosaicism Uncovers Inheritance of an Apparently De Novo GFAP Mutation

TGF-β1, Ghrelin, Neurexin, and Neuroligin are Predictive Biomarkers for Postoperative Prognosis of Laparoscopic Surgery in Children with Hirschsprung Disease

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