Signatures of miR-181a on renal transcriptome and blood pressure.

Francine Z Marques; Simon P R Romaine; Matthew Denniff; James Eales; John Dormer; Ingrid M Garrelds; Lukasz Wojnar; Katarzyna Musialik; Barbara Duda-Raszewska; Bartlomiej Kiszka; Magdalena Duda; Brian J Morris; Nilesh J Samani; A H Jan Danser; Pawel Bogdanski; Ewa Zukowska-Szczechowska; Fadi J Charchar; Maciej Tomaszewski

doi:10.2119/molmed.2015.00096

Signatures of miR-181a on renal transcriptome and blood pressure.

Francine Z Marques
, Simon P R Romaine
, Matthew Denniff
, James Eales
, John Dormer
, Ingrid M Garrelds
, Lukasz Wojnar
, Katarzyna Musialik
, Barbara Duda-Raszewska
, Bartlomiej Kiszka
, Magdalena Duda
, Brian J Morris
, Nilesh J Samani
, A H Jan Danser
, Pawel Bogdanski
, Ewa Zukowska-Szczechowska
, Fadi J Charchar
, Maciej Tomaszewski

Research output: Contribution to journal › Article › peer-review

Abstract

MicroRNA-181a binds to the 3' untranslated region of messenger RNA (mRNA) for renin, a rate-limiting enzyme of the renin-angiotensin system. Our objective was to determine whether this molecular interaction translates into a clinically meaningful effect on blood pressure and whether circulating miR-181a is a measurable proxy of blood pressure. In 200 human kidneys from the TRANScriptome of renaL humAn TissuE (TRANSLATE) Study, renal miR-181a was the sole negative predictor of renin mRNA and a strong correlate of circulating miR-181a. Elevated miR-181a levels correlated positively with systolic and diastolic blood pressure in TRANSLATE, and this association was independent of circulating renin. The association between serum miR-181a and systolic blood pressure was replicated in 199 subjects from the Genetic Regulation of Arterial Pressure of Humans In the Community (GRAPHIC) Study. Renal immunohistochemistry and in situ hybridization showed that co-localization of miR-181a and renin was most prominent in collecting ducts from where renin is not released into the systemic circulation. Analysis of 69 human kidneys characterized by RNA-sequencing revealed that miR-181a was associated with down-regulation of four mitochondrial pathways and up-regulation of 41 signalling cascades of adaptive immunity and inflammation. We conclude that renal miR-181a has pleiotropic effects on pathways relevant to blood pressure regulation and that circulating levels of miR-181a are both a measurable proxy of renal miR-181a expression and a novel biochemical correlate of blood pressure.

Original language	English
Journal	Molecular medicine (Cambridge, Mass.)
DOIs	https://doi.org/10.2119/molmed.2015.00096
Publication status	Published - 24 Aug 2015

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Marques, F. Z., Romaine, S. P. R., Denniff, M., Eales, J., Dormer, J., Garrelds, I. M., Wojnar, L., Musialik, K., Duda-Raszewska, B., Kiszka, B., Duda, M., Morris, B. J., Samani, N. J., Danser, A. H. J., Bogdanski, P., Zukowska-Szczechowska, E., Charchar, F. J., & Tomaszewski, M. (2015). Signatures of miR-181a on renal transcriptome and blood pressure. Molecular medicine (Cambridge, Mass.). https://doi.org/10.2119/molmed.2015.00096

@article{f364f3d2136e41f0b47217fec1412e8a,

title = "Signatures of miR-181a on renal transcriptome and blood pressure.",

abstract = "MicroRNA-181a binds to the 3' untranslated region of messenger RNA (mRNA) for renin, a rate-limiting enzyme of the renin-angiotensin system. Our objective was to determine whether this molecular interaction translates into a clinically meaningful effect on blood pressure and whether circulating miR-181a is a measurable proxy of blood pressure. In 200 human kidneys from the TRANScriptome of renaL humAn TissuE (TRANSLATE) Study, renal miR-181a was the sole negative predictor of renin mRNA and a strong correlate of circulating miR-181a. Elevated miR-181a levels correlated positively with systolic and diastolic blood pressure in TRANSLATE, and this association was independent of circulating renin. The association between serum miR-181a and systolic blood pressure was replicated in 199 subjects from the Genetic Regulation of Arterial Pressure of Humans In the Community (GRAPHIC) Study. Renal immunohistochemistry and in situ hybridization showed that co-localization of miR-181a and renin was most prominent in collecting ducts from where renin is not released into the systemic circulation. Analysis of 69 human kidneys characterized by RNA-sequencing revealed that miR-181a was associated with down-regulation of four mitochondrial pathways and up-regulation of 41 signalling cascades of adaptive immunity and inflammation. We conclude that renal miR-181a has pleiotropic effects on pathways relevant to blood pressure regulation and that circulating levels of miR-181a are both a measurable proxy of renal miR-181a expression and a novel biochemical correlate of blood pressure.",

author = "Marques, \{Francine Z\} and Romaine, \{Simon P R\} and Matthew Denniff and James Eales and John Dormer and Garrelds, \{Ingrid M\} and Lukasz Wojnar and Katarzyna Musialik and Barbara Duda-Raszewska and Bartlomiej Kiszka and Magdalena Duda and Morris, \{Brian J\} and Samani, \{Nilesh J\} and Danser, \{A H Jan\} and Pawel Bogdanski and Ewa Zukowska-Szczechowska and Charchar, \{Fadi J\} and Maciej Tomaszewski",

year = "2015",

month = aug,

day = "24",

doi = "10.2119/molmed.2015.00096",

language = "English",

journal = "Molecular medicine (Cambridge, Mass.)",

issn = "1528-3658",

publisher = "Feinstein Institute for Medical Research",

}

Marques, FZ, Romaine, SPR, Denniff, M, Eales, J, Dormer, J, Garrelds, IM, Wojnar, L, Musialik, K, Duda-Raszewska, B, Kiszka, B, Duda, M, Morris, BJ, Samani, NJ, Danser, AHJ, Bogdanski, P, Zukowska-Szczechowska, E, Charchar, FJ & Tomaszewski, M 2015, 'Signatures of miR-181a on renal transcriptome and blood pressure.', Molecular medicine (Cambridge, Mass.). https://doi.org/10.2119/molmed.2015.00096

TY - JOUR

T1 - Signatures of miR-181a on renal transcriptome and blood pressure.

AU - Marques, Francine Z

AU - Romaine, Simon P R

AU - Denniff, Matthew

AU - Eales, James

AU - Dormer, John

AU - Garrelds, Ingrid M

AU - Wojnar, Lukasz

AU - Musialik, Katarzyna

AU - Duda-Raszewska, Barbara

AU - Kiszka, Bartlomiej

AU - Duda, Magdalena

AU - Morris, Brian J

AU - Samani, Nilesh J

AU - Danser, A H Jan

AU - Bogdanski, Pawel

AU - Zukowska-Szczechowska, Ewa

AU - Charchar, Fadi J

AU - Tomaszewski, Maciej

PY - 2015/8/24

Y1 - 2015/8/24

N2 - MicroRNA-181a binds to the 3' untranslated region of messenger RNA (mRNA) for renin, a rate-limiting enzyme of the renin-angiotensin system. Our objective was to determine whether this molecular interaction translates into a clinically meaningful effect on blood pressure and whether circulating miR-181a is a measurable proxy of blood pressure. In 200 human kidneys from the TRANScriptome of renaL humAn TissuE (TRANSLATE) Study, renal miR-181a was the sole negative predictor of renin mRNA and a strong correlate of circulating miR-181a. Elevated miR-181a levels correlated positively with systolic and diastolic blood pressure in TRANSLATE, and this association was independent of circulating renin. The association between serum miR-181a and systolic blood pressure was replicated in 199 subjects from the Genetic Regulation of Arterial Pressure of Humans In the Community (GRAPHIC) Study. Renal immunohistochemistry and in situ hybridization showed that co-localization of miR-181a and renin was most prominent in collecting ducts from where renin is not released into the systemic circulation. Analysis of 69 human kidneys characterized by RNA-sequencing revealed that miR-181a was associated with down-regulation of four mitochondrial pathways and up-regulation of 41 signalling cascades of adaptive immunity and inflammation. We conclude that renal miR-181a has pleiotropic effects on pathways relevant to blood pressure regulation and that circulating levels of miR-181a are both a measurable proxy of renal miR-181a expression and a novel biochemical correlate of blood pressure.

AB - MicroRNA-181a binds to the 3' untranslated region of messenger RNA (mRNA) for renin, a rate-limiting enzyme of the renin-angiotensin system. Our objective was to determine whether this molecular interaction translates into a clinically meaningful effect on blood pressure and whether circulating miR-181a is a measurable proxy of blood pressure. In 200 human kidneys from the TRANScriptome of renaL humAn TissuE (TRANSLATE) Study, renal miR-181a was the sole negative predictor of renin mRNA and a strong correlate of circulating miR-181a. Elevated miR-181a levels correlated positively with systolic and diastolic blood pressure in TRANSLATE, and this association was independent of circulating renin. The association between serum miR-181a and systolic blood pressure was replicated in 199 subjects from the Genetic Regulation of Arterial Pressure of Humans In the Community (GRAPHIC) Study. Renal immunohistochemistry and in situ hybridization showed that co-localization of miR-181a and renin was most prominent in collecting ducts from where renin is not released into the systemic circulation. Analysis of 69 human kidneys characterized by RNA-sequencing revealed that miR-181a was associated with down-regulation of four mitochondrial pathways and up-regulation of 41 signalling cascades of adaptive immunity and inflammation. We conclude that renal miR-181a has pleiotropic effects on pathways relevant to blood pressure regulation and that circulating levels of miR-181a are both a measurable proxy of renal miR-181a expression and a novel biochemical correlate of blood pressure.

U2 - 10.2119/molmed.2015.00096

DO - 10.2119/molmed.2015.00096

M3 - Article

C2 - 26322847

SN - 1528-3658

JO - Molecular medicine (Cambridge, Mass.)

JF - Molecular medicine (Cambridge, Mass.)

ER -

Signatures of miR-181a on renal transcriptome and blood pressure.

Abstract

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