Dysregulation of Principal Cell miRNAs Facilitates Epigenetic Regulation of AQP2 and Results in Nephrogenic Diabetes Insipidus

Publikationstyp:
Zeitschriftenaufsatz
Metadaten:
Autoren
  • Federica Petrillo
  • Anna Iervolino
  • Tiziana Angrisano
  • Sabina Jelen
  • Vincenzo Costanzo
  • Mariavittoria DAcierno
  • Lei Cheng
  • Qi Wu
  • Ilaria Guerriero
  • Maria Cristina Mazzarella
  • Alfonso De Falco
  • Fulvio DAngelo
  • Michele Ceccarelli
  • Michele Caraglia
  • Giovambattista Capasso
  • Robert AA Fenton
  • Francesco Trepiccione
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000988595000011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=7c6cbd95cc08067bf5cec85ffdc20efd
DOI
10.1681/ASN.2020010031
eISSN
1533-3450
Externe Identifier
  • Clarivate Analytics Document Solution ID: VM2TX
ISSN
1046-6673
Ausgabe der Veröffentlichung
6
Zeitschrift
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
Schlüsselwörter
  • AQP2
  • Dicer
  • miRNA
  • ENaC
  • DNA methylation
  • epigenetics
Paginierung
1339 - 1354
Datum der Veröffentlichung
2021
Status
Published
Titel
Dysregulation of Principal Cell miRNAs Facilitates Epigenetic Regulation of AQP2 and Results in Nephrogenic Diabetes Insipidus
Sub types
  • Article
Ausgabe der Zeitschrift
32

Datenquelle: Web of Science (Lite)

Andere Metadatenquellen:
Autoren
  • Federica Petrillo
  • Anna Iervolino
  • Tiziana Angrisano
  • Sabina Jelen
  • Vincenzo Costanzo
  • Mariavittoria D'Acierno
  • Lei Cheng
  • Qi Wu
  • Ilaria Guerriero
  • Maria Cristina Mazzarella
  • Alfonso De Falco
  • Fulvio D'Angelo
  • Michele Ceccarelli
  • Michele Caraglia
  • Giovambattista Capasso
  • Robert A Fenton
  • Francesco Trepiccione
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000664206100010&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1681/ASN.2020010031
eISSN
1533-3450
Externe Identifier
  • Clarivate Analytics Document Solution ID: SW0KP
  • PubMed Identifier: 33727367
ISSN
1046-6673
Ausgabe der Veröffentlichung
6
Zeitschrift
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
Paginierung
1339 - 1354
Datum der Veröffentlichung
2021
Status
Published
Titel
Dysregulation of Principal Cell miRNAs Facilitates Epigenetic Regulation of AQP2 and Results in Nephrogenic Diabetes Insipidus
Sub types
  • Article
Ausgabe der Zeitschrift
32

Datenquelle: Web of Science (Lite)

Abstract
<jats:sec> <jats:title>Significance Statement</jats:title> <jats:p>Water reabsorption along the collecting duct is dependent on the function of aquaporin 2 (AQP2). Currently, information on microRNA (miRNA)-mediated, post-transcriptional regulation of AQP2, which may influence water reabsorption, is limited. In mice, ablation of the Dicer enzyme (crucial for miRNA maturation) in AQP2-expressing cells induces nephrogenic diabetes insipidus (NDI) with dysregulation of the miRNA profile. A major finding is the identification of miRNAs associated with NDI through mediating epigenetic control of AQP2. This study offers novel targets for AQP2 regulation and potential treatment for governing renal water reabsorption.</jats:p> </jats:sec> <jats:sec> <jats:title>Background</jats:title> <jats:p>MicroRNAs (miRNAs), formed by cleavage of pre-microRNA by the endoribonuclease Dicer, are critical modulators of cell function by post-transcriptionally regulating gene expression.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Selective ablation of Dicer in AQP2-expressing cells (Dicer<jats:sup>AQP2Cre+</jats:sup> mice) was used to investigate the role of miRNAs in the kidney collecting duct of mice.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>The mice had severe polyuria and nephrogenic diabetes insipidus, potentially due to greatly reduced AQP2 and AQP4 levels. Although epithelial sodium channel levels were decreased in cortex and increased in inner medulla, amiloride-sensitive sodium reabsorption was equivalent in Dicer<jats:sup>AQP2Cre+</jats:sup> mice and controls. Small-RNA sequencing and proteomic analysis revealed 31 and 178 significantly regulated miRNAs and proteins, respectively. Integrated bioinformatic analysis of the miRNAome and proteome suggested alterations in the epigenetic machinery and various transcription factors regulating AQP2 expression in Dicer<jats:sup>AQP2Cre+</jats:sup> mice. The expression profile and function of three miRNAs (miR-7688-5p, miR-8114, and miR-409-3p) whose predicted targets were involved in epigenetic control (Phf2, Kdm5c, and Kdm4a) or transcriptional regulation (GATA3, GATA2, and ELF3) of AQP2 were validated. Luciferase assays could not demonstrate direct interaction of AQP2 or the three potential transcription factors with miR-7688-5p, miR-8114, and miR-409–3p. However, transfection of respective miRNA mimics reduced AQP2 expression. Chromatin immunoprecipitation assays demonstrated decreased Phf2 and significantly increased Kdm5c interactions at the <jats:italic toggle="yes">Aqp2</jats:italic> gene promoter in Dicer<jats:sup>AQP2Cre+</jats:sup> mice, resulting in decreased RNA Pol II association.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Novel evidence indicates miRNA-mediated epigenetic regulation of AQP2 expression.</jats:p> </jats:sec>
Autoren
  • Federica Petrillo
  • Anna Iervolino
  • Tiziana Angrisano
  • Sabina Jelen
  • Vincenzo Costanzo
  • Mariavittoria D’Acierno
  • Lei Cheng
  • Qi Wu
  • Ilaria Guerriero
  • Maria Cristina Mazzarella
  • Alfonso De Falco
  • Fulvio D’Angelo
  • Michele Ceccarelli
  • Michele Caraglia
  • Giovambattista Capasso
  • Robert A Fenton
  • Francesco Trepiccione
DOI
10.1681/asn.2020010031
eISSN
1533-3450
ISSN
1046-6673
Ausgabe der Veröffentlichung
6
Zeitschrift
Journal of the American Society of Nephrology
Sprache
en
Online publication date
2021
Paginierung
1339 - 1354
Datum der Veröffentlichung
2021
Status
Published
Herausgeber
Ovid Technologies (Wolters Kluwer Health)
Herausgeber URL
http://dx.doi.org/10.1681/asn.2020010031
Datum der Datenerfassung
2023
Titel
Dysregulation of Principal Cell miRNAs Facilitates Epigenetic Regulation of AQP2 and Results in Nephrogenic Diabetes Insipidus
Ausgabe der Zeitschrift
32

Datenquelle: Crossref

Abstract
<h4>Background</h4>MicroRNAs (miRNAs), formed by cleavage of pre-microRNA by the endoribonuclease Dicer, are critical modulators of cell function by post-transcriptionally regulating gene expression.<h4>Methods</h4>Selective ablation of Dicer in AQP2-expressing cells (Dicer<sup>AQP2Cre+</sup> mice) was used to investigate the role of miRNAs in the kidney collecting duct of mice.<h4>Results</h4>The mice had severe polyuria and nephrogenic diabetes insipidus, potentially due to greatly reduced AQP2 and AQP4 levels. Although epithelial sodium channel levels were decreased in cortex and increased in inner medulla, amiloride-sensitive sodium reabsorption was equivalent in Dicer<sup>AQP2Cre+</sup> mice and controls. Small-RNA sequencing and proteomic analysis revealed 31 and 178 significantly regulated miRNAs and proteins, respectively. Integrated bioinformatic analysis of the miRNAome and proteome suggested alterations in the epigenetic machinery and various transcription factors regulating AQP2 expression in Dicer<sup>AQP2Cre+</sup> mice. The expression profile and function of three miRNAs (miR-7688-5p, miR-8114, and miR-409-3p) whose predicted targets were involved in epigenetic control (Phf2, Kdm5c, and Kdm4a) or transcriptional regulation (GATA3, GATA2, and ELF3) of AQP2 were validated. Luciferase assays could not demonstrate direct interaction of AQP2 or the three potential transcription factors with miR-7688-5p, miR-8114, and miR-409-3p. However, transfection of respective miRNA mimics reduced AQP2 expression. Chromatin immunoprecipitation assays demonstrated decreased Phf2 and significantly increased Kdm5c interactions at the <i>Aqp2</i> gene promoter in Dicer<sup>AQP2Cre+</sup> mice, resulting in decreased RNA Pol II association.<h4>Conclusions</h4>Novel evidence indicates miRNA-mediated epigenetic regulation of AQP2 expression.
Addresses
  • Biogem, Institute of Genetic Research "Gaetano Salvatore", Ariano Irpino, Italy.
Autoren
  • Federica Petrillo
  • Anna Iervolino
  • Tiziana Angrisano
  • Sabina Jelen
  • Vincenzo Costanzo
  • Mariavittoria D'Acierno
  • Lei Cheng
  • Qi Wu
  • Ilaria Guerriero
  • Maria Cristina Mazzarella
  • Alfonso De Falco
  • Fulvio D'Angelo
  • Michele Ceccarelli
  • Michele Caraglia
  • Giovambattista Capasso
  • Robert A Fenton
  • Francesco Trepiccione
DOI
10.1681/asn.2020010031
eISSN
1533-3450
Externe Identifier
  • PubMed Identifier: 33727367
  • PubMed Central ID: PMC8259636
Funding acknowledgements
  • Novo Nordisk Fonden: NNF19OC0058439
  • Novo Nordisk Fonden: NNF17OC0028812
  • Novo Nordisk Fonden: NNF18OC0031686
  • Novo Nordisk Fonden: NNF20OC0063837
Open access
false
ISSN
1046-6673
Ausgabe der Veröffentlichung
6
Zeitschrift
Journal of the American Society of Nephrology : JASN
Schlüsselwörter
  • Kidney Tubules, Collecting
  • Animals
  • Mice
  • Diabetes Insipidus, Nephrogenic
  • Polyuria
  • Ribonuclease III
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Proteome
  • Transcription Factors
  • MicroRNAs
  • Sequence Analysis, RNA
  • Gene Expression Regulation
  • Down-Regulation
  • Epigenesis, Genetic
  • RNA Processing, Post-Transcriptional
  • Female
  • Male
  • GATA2 Transcription Factor
  • GATA3 Transcription Factor
  • Aquaporin 2
  • Histone Demethylases
  • Epithelial Sodium Channels
  • Renal Reabsorption
Sprache
eng
Medium
Print-Electronic
Online publication date
2021
Paginierung
1339 - 1354
Datum der Veröffentlichung
2021
Status
Published
Datum der Datenerfassung
2021
Titel
Dysregulation of Principal Cell miRNAs Facilitates Epigenetic Regulation of AQP2 and Results in Nephrogenic Diabetes Insipidus.
Sub types
  • Research Support, Non-U.S. Gov't
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
32

Datenquelle: Europe PubMed Central

Abstract
BACKGROUND: MicroRNAs (miRNAs), formed by cleavage of pre-microRNA by the endoribonuclease Dicer, are critical modulators of cell function by post-transcriptionally regulating gene expression. METHODS: Selective ablation of Dicer in AQP2-expressing cells (DicerAQP2Cre+ mice) was used to investigate the role of miRNAs in the kidney collecting duct of mice. RESULTS: The mice had severe polyuria and nephrogenic diabetes insipidus, potentially due to greatly reduced AQP2 and AQP4 levels. Although epithelial sodium channel levels were decreased in cortex and increased in inner medulla, amiloride-sensitive sodium reabsorption was equivalent in DicerAQP2Cre+ mice and controls. Small-RNA sequencing and proteomic analysis revealed 31 and 178 significantly regulated miRNAs and proteins, respectively. Integrated bioinformatic analysis of the miRNAome and proteome suggested alterations in the epigenetic machinery and various transcription factors regulating AQP2 expression in DicerAQP2Cre+ mice. The expression profile and function of three miRNAs (miR-7688-5p, miR-8114, and miR-409-3p) whose predicted targets were involved in epigenetic control (Phf2, Kdm5c, and Kdm4a) or transcriptional regulation (GATA3, GATA2, and ELF3) of AQP2 were validated. Luciferase assays could not demonstrate direct interaction of AQP2 or the three potential transcription factors with miR-7688-5p, miR-8114, and miR-409-3p. However, transfection of respective miRNA mimics reduced AQP2 expression. Chromatin immunoprecipitation assays demonstrated decreased Phf2 and significantly increased Kdm5c interactions at the Aqp2 gene promoter in DicerAQP2Cre+ mice, resulting in decreased RNA Pol II association. CONCLUSIONS: Novel evidence indicates miRNA-mediated epigenetic regulation of AQP2 expression.
Date of acceptance
2021
Autoren
  • Federica Petrillo
  • Anna Iervolino
  • Tiziana Angrisano
  • Sabina Jelen
  • Vincenzo Costanzo
  • Mariavittoria D'Acierno
  • Lei Cheng
  • Qi Wu
  • Ilaria Guerriero
  • Maria Cristina Mazzarella
  • Alfonso De Falco
  • Fulvio D'Angelo
  • Michele Ceccarelli
  • Michele Caraglia
  • Giovambattista Capasso
  • Robert A Fenton
  • Francesco Trepiccione
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/33727367
DOI
10.1681/ASN.2020010031
eISSN
1533-3450
Externe Identifier
  • PubMed Central ID: PMC8259636
Ausgabe der Veröffentlichung
6
Zeitschrift
J Am Soc Nephrol
Schlüsselwörter
  • AQP2
  • DNA methylation
  • Dicer
  • ENaC
  • epigenetics
  • miRNA
  • Animals
  • Aquaporin 2
  • DNA-Binding Proteins
  • Diabetes Insipidus, Nephrogenic
  • Down-Regulation
  • Epigenesis, Genetic
  • Epithelial Sodium Channels
  • Female
  • GATA2 Transcription Factor
  • GATA3 Transcription Factor
  • Gene Expression Regulation
  • Histone Demethylases
  • Homeodomain Proteins
  • Kidney Tubules, Collecting
  • Male
  • Mice
  • MicroRNAs
  • Polyuria
  • Proteome
  • RNA Processing, Post-Transcriptional
  • Renal Reabsorption
  • Ribonuclease III
  • Sequence Analysis, RNA
  • Transcription Factors
Sprache
eng
Country
United States
Paginierung
1339 - 1354
PII
00001751-202106000-00011
Datum der Veröffentlichung
2021
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2021
Titel
Dysregulation of Principal Cell miRNAs Facilitates Epigenetic Regulation of AQP2 and Results in Nephrogenic Diabetes Insipidus.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
32

Datenquelle: PubMed

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