Deficiency of MicroRNA-181a Results in Transcriptome-Wide Cell Specific Changes in the Kidney that Lead to Elevated Blood Pressure and Salt Sensitivity Article Swipe
Madeleine Paterson
,
Kristy L. Jackson
,
Malathi S.I. Dona
,
Gabriella E. Farrugia
,
Bruna Visniauskas
,
Anna M.D. Watson
,
Chad Johnson
,
Minolfa C. Prieto
,
Roger G. Evans
,
Fadi J. Charchar
,
Alexander R. Pinto
,
Francine Z. Marques
,
Geoffrey A. Head
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1101/2021.03.18.436092
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1101/2021.03.18.436092
MicroRNA miR-181a is down-regulated in the kidneys of hypertensive patients and hypertensive mice. In vitro , miR-181a is a posttranslational inhibitor of renin expression, but pleiotropic mechanisms by which miR-181a may influence blood pressure (BP) are unknown. Here we determined whether deletion of miR-181a/b-1 in vivo changes BP and the molecular mechanisms involved at the single-cell level. We developed a knockout mouse model lacking miR-181a/b-1 genes using CRISPR/Cas9 technology. Radio-telemetry probes were implanted in twelve-week-old C57BL/6J wild-type and miR-181a/b-1 knockout mice. Systolic and diastolic BP were 4-5mmHg higher in knockout compared with wild-type mice over 24-hours ( P<0 . 01 ). Compared with wild-type mice, renal renin was higher in the juxtaglomerular cells of knockout mice. BP was similar in wild-type mice on a high (3.1%) versus low (0.3%) sodium diet (+0.4±0.8mmHg) but knockout mice showed salt sensitivity (+3.3±0.8mmHg, P<0 . 001 ). Since microRNAs can target several mRNAs simultaneously, we performed single-nuclei RNA-sequencing in 6,699 renal cells. We identified 12 distinct types of renal cells, all of which had genes that were dysregulated. This included genes involved in renal fibrosis and inflammation such as Stat4, Col4a1, Cd81, Flt3l, Cxcl16, Smad4 . We observed up-regulation of pathways related to the immune system, inflammatory response, reactive oxygen species and nerve development, consistent with higher tyrosine hydroxylase. In conclusion, downregulation of the miR-181a gene led to increased BP and salt sensitivity in mice. This is likely due to an increase in renin expression in juxtaglomerular cells, as well as microRNA-driven pleiotropic effects impacting renal pathways associated with hypertension.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2021.03.18.436092
- https://www.biorxiv.org/content/biorxiv/early/2021/03/19/2021.03.18.436092.full.pdf
- OA Status
- green
- References
- 42
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3138970939
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- OpenAlex ID
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https://openalex.org/W3138970939Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2021.03.18.436092Digital Object Identifier
- Title
-
Deficiency of MicroRNA-181a Results in Transcriptome-Wide Cell Specific Changes in the Kidney that Lead to Elevated Blood Pressure and Salt SensitivityWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-03-19Full publication date if available
- Authors
-
Madeleine Paterson, Kristy L. Jackson, Malathi S.I. Dona, Gabriella E. Farrugia, Bruna Visniauskas, Anna M.D. Watson, Chad Johnson, Minolfa C. Prieto, Roger G. Evans, Fadi J. Charchar, Alexander R. Pinto, Francine Z. Marques, Geoffrey A. HeadList of authors in order
- Landing page
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https://doi.org/10.1101/2021.03.18.436092Publisher landing page
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https://www.biorxiv.org/content/biorxiv/early/2021/03/19/2021.03.18.436092.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
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https://www.biorxiv.org/content/biorxiv/early/2021/03/19/2021.03.18.436092.full.pdfDirect OA link when available
- Concepts
-
Knockout mouse, Kidney, microRNA, Inflammation, Renin–angiotensin system, Downregulation and upregulation, Internal medicine, Endocrinology, Biology, Blood pressure, Gene knockout, Wild type, Afferent arterioles, Gene, Medicine, Receptor, Genetics, MutantTop concepts (fields/topics) attached by OpenAlex
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0Total citation count in OpenAlex
- References (count)
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42Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.implanted | 73 |
| abstract_inverted_index.increased | 225 |
| abstract_inverted_index.influence | 32 |
| abstract_inverted_index.inhibitor | 21 |
| abstract_inverted_index.microRNAs | 145 |
| abstract_inverted_index.molecular | 51 |
| abstract_inverted_index.performed | 152 |
| abstract_inverted_index.response, | 204 |
| abstract_inverted_index.wild-type | 77, 93, 104, 121 |
| abstract_inverted_index.associated | 254 |
| abstract_inverted_index.consistent | 211 |
| abstract_inverted_index.determined | 40 |
| abstract_inverted_index.expression | 241 |
| abstract_inverted_index.identified | 160 |
| abstract_inverted_index.mechanisms | 27, 52 |
| abstract_inverted_index.CRISPR/Cas9 | 68 |
| abstract_inverted_index.conclusion, | 217 |
| abstract_inverted_index.expression, | 24 |
| abstract_inverted_index.pleiotropic | 26, 249 |
| abstract_inverted_index.sensitivity | 138, 229 |
| abstract_inverted_index.single-cell | 56 |
| abstract_inverted_index.technology. | 69 |
| abstract_inverted_index.development, | 210 |
| abstract_inverted_index.hydroxylase. | 215 |
| abstract_inverted_index.hypertensive | 9, 12 |
| abstract_inverted_index.inflammation | 183 |
| abstract_inverted_index.inflammatory | 203 |
| abstract_inverted_index.miR-181a/b-1 | 44, 65, 79 |
| abstract_inverted_index.dysregulated. | 174 |
| abstract_inverted_index.hypertension. | 256 |
| abstract_inverted_index.single-nuclei | 153 |
| abstract_inverted_index.up-regulation | 195 |
| abstract_inverted_index.RNA-sequencing | 154 |
| abstract_inverted_index.down-regulated | 4 |
| abstract_inverted_index.downregulation | 218 |
| abstract_inverted_index.(+0.4±0.8mmHg) | 132 |
| abstract_inverted_index.(+3.3±0.8mmHg, | 139 |
| abstract_inverted_index.Radio-telemetry | 70 |
| abstract_inverted_index.juxtaglomerular | 112, 243 |
| abstract_inverted_index.microRNA-driven | 248 |
| abstract_inverted_index.simultaneously, | 150 |
| abstract_inverted_index.twelve-week-old | 75 |
| abstract_inverted_index.posttranslational | 20 |
| cited_by_percentile_year | |
| countries_distinct_count | 2 |
| institutions_distinct_count | 13 |
| citation_normalized_percentile.value | 0.03078842 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |