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dc.contributor.authorPapagregoriou, Gregory N.en
dc.contributor.authorErguler, K.en
dc.contributor.authorDweep, H.en
dc.contributor.authorVoskarides, Konstantinosen
dc.contributor.authorKoupepidou, P.en
dc.contributor.authorAthanasiou, Yiannisen
dc.contributor.authorPierides, Alkis M.en
dc.contributor.authorGretz, N.en
dc.contributor.authorFelekkis, Kyriacos N.en
dc.contributor.authorConstantinou-Deltas, Constantinos D.en
dc.creatorPapagregoriou, Gregory N.en
dc.creatorErguler, K.en
dc.creatorDweep, H.en
dc.creatorVoskarides, Konstantinosen
dc.creatorKoupepidou, P.en
dc.creatorAthanasiou, Yiannisen
dc.creatorPierides, Alkis M.en
dc.creatorGretz, N.en
dc.creatorFelekkis, Kyriacos N.en
dc.creatorConstantinou-Deltas, Constantinos D.en
dc.date.accessioned2019-11-04T12:52:26Z
dc.date.available2019-11-04T12:52:26Z
dc.date.issued2012
dc.identifier.issn1932-6203
dc.identifier.urihttp://gnosis.library.ucy.ac.cy/handle/7/53286
dc.description.abstractHeparin binding epidermal growth factor (HBEGF) is expressed in podocytes and was shown to play a role in glomerular physiology. MicroRNA binding sites on the 3′UTR of HBEGF were predicted using miRWalk algorithm and followed by DNA sequencing in 103 patients diagnosed with mild or severe glomerulopathy. A single nucleotide polymorphism, miRSNP C1936T (rs13385), was identified at the 3′UTR of HBEGF that corresponds to the second base of the hsa-miR-1207-5p seed region. When AB8/13 undifferentiated podocytes were transfected with miRNA mimics of hsa-miR-1207-5p, the HBEGF protein levels were reduced by about 50%. A DNA fragment containing the miRSNP allele-1936C was cloned into the pMIR-Report Luciferase vector and co-transfected with miRNA mimics of hsa-miR-1207-5p into AB8/13 podocytes. In agreement with western blot data, this resulted in reduced luciferase expression demonstrating the ability of hsa-miR-1207-5p to directly regulate HBEGF expression. On the contrary, in the presence of the miRSNP 1936T allele, this regulation was abolished. Collectively, these results demonstrate that variant 1936T of this miRSNP prevents hsa-miR-1207-5p from down-regulating HBEGF in podocytes. We hypothesized that this variant has a functional role as a genetic modifier. To this end, we showed that in a cohort of 78 patients diagnosed with CFHR5 nephropathy (also known as C3-glomerulopathy), inheritance of miRSNP 1936T allele was significantly increased in the group demonstrating progression to chronic renal failure on long follow-up. No similar association was detected in a cohort of patients with thin basement membrane nephropathy. This is the first report associating a miRSNP as genetic modifier to a monogenic renal disorder. © 2012 Papagregoriou et al.en
dc.sourcePLoS ONEen
dc.source.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84856485045&doi=10.1371%2fjournal.pone.0031021&partnerID=40&md5=5239b17c21a2721547a50469af6876ab
dc.subjectarticleen
dc.subjecthumanen
dc.subjectHumansen
dc.subjectcontrolled studyen
dc.subjectDisease Progressionen
dc.subjectfollow upen
dc.subjectdisease courseen
dc.subject3' untranslated regionen
dc.subjectalleleen
dc.subjectgeneen
dc.subjectgenetic associationen
dc.subjectsingle nucleotide polymorphismen
dc.subjectgenotypeen
dc.subjectgenetic polymorphismen
dc.subjectunclassified drugen
dc.subjecthospitalizationen
dc.subjectdown regulationen
dc.subjectgene expression regulationen
dc.subjectdisease severityen
dc.subjectkidney diseaseen
dc.subjecthuman cellen
dc.subjectmicroRNAen
dc.subjectgeneticsen
dc.subjectComplement System Proteinsen
dc.subjectSeverity of Illness Indexen
dc.subjectMicroRNAsen
dc.subjectDNA fragmenten
dc.subjectIntercellular Signaling Peptides and Proteinsen
dc.subjectpredictive valueen
dc.subjectDNA sequenceen
dc.subjectgene identificationen
dc.subjectchronic kidney failureen
dc.subjectgenetic algorithmen
dc.subjectbioinformaticsen
dc.subjectPolymorphism, Geneticen
dc.subjectgenetic transfectionen
dc.subjectWestern blottingen
dc.subjectKidney Failure, Chronicen
dc.subjectglomerulopathyen
dc.subjectmarker geneen
dc.subjectmolecular cloningen
dc.subjectCFHR5 geneen
dc.subjectGlomerulonephritis, Membranousen
dc.subjectmembranous glomerulonephritisen
dc.subjectbinding siteen
dc.subjectBinding Sitesen
dc.subjectreporter geneen
dc.subjectpodocyteen
dc.subjectgene therapyen
dc.subjectsignal peptideen
dc.subjectluciferaseen
dc.subjectcomplementen
dc.subjectFHR5 protein, humanen
dc.subjectHBEGF geneen
dc.subjectheparin binding epidermal growth factoren
dc.subjectheparin-binding EGF-like growth factoren
dc.subjectmicroRNA 1207 5pen
dc.subjectMIRN1207 microRNA, humanen
dc.titleA miR-1207-5p binding site polymorphism abolishes regulation of HBEGF and is associated with disease severity in CFHR5 nephropathyen
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1371/journal.pone.0031021
dc.description.volume7
dc.author.facultyΣχολή Θετικών και Εφαρμοσμένων Επιστημών / Faculty of Pure and Applied Sciences
dc.author.departmentΤμήμα Βιολογικών Επιστημών / Department of Biological Sciences
dc.type.uhtypeArticleen
dc.description.notes<p>Cited By :30</p>en
dc.source.abbreviationPLoS ONEen
dc.contributor.orcidConstantinou-Deltas, Constantinos D. [0000-0001-5549-9169]
dc.gnosis.orcid0000-0001-5549-9169


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