Identification of Hypothalamic Long Noncoding RNAs Associated with Hypertension and the Behavior/Neurological Phenotype of Hypertensive ISIAH Rats

Larisa A Fedoseeva; Nikita I Ershov; Ivan A Sidorenko; Arcady L Markel; Olga E Redina

doi:10.3390/genes13091598

Identification of Hypothalamic Long Noncoding RNAs Associated with Hypertension and the Behavior/Neurological Phenotype of Hypertensive ISIAH Rats

Genes (Basel). 2022 Sep 7;13(9):1598. doi: 10.3390/genes13091598.

Authors

Larisa A Fedoseeva¹, Nikita I Ershov¹, Ivan A Sidorenko¹, Arcady L Markel¹, Olga E Redina¹

Affiliation

¹ Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia.

Abstract

Long noncoding RNAs (lncRNAs) play an important role in the control of many physiological and pathophysiological processes, including the development of hypertension and other cardiovascular diseases. Nonetheless, the understanding of the regulatory function of many lncRNAs is still incomplete. This work is a continuation of our earlier study on the sequencing of hypothalamic transcriptomes of hypertensive ISIAH rats and control normotensive WAG rats. It aims to identify lncRNAs that may be involved in the formation of the hypertensive state and the associated behavioral features of ISIAH rats. Interstrain differences in the expression of seven lncRNAs were validated by quantitative PCR. Differential hypothalamic expression of lncRNAs LOC100910237 and RGD1562890 between hypertensive and normotensive rats was shown for the first time. Expression of four lncRNAs (Snhg4, LOC100910237, RGD1562890, and Tnxa-ps1) correlated with transcription levels of many hypothalamic genes differentially expressed between ISIAH and WAG rats (DEGs), including genes associated with the behavior/neurological phenotype and hypertension. After functional annotation of these DEGs, it was concluded that lncRNAs Snhg4, LOC100910237, RGD1562890, and Tnxa-ps1 may be involved in the hypothalamic processes related to immune-system functioning and in the response to various exogenous and endogenous factors, including hormonal stimuli. Based on the functional enrichment analysis of the networks, an association of lncRNAs LOC100910237 and Tnxa-ps1 with retinol metabolism and an association of lncRNAs RGD1562890 and Tnxa-ps1 with type 1 diabetes mellitus are proposed for the first time. Based on a discussion, it is hypothesized that previously functionally uncharacterized lncRNA LOC100910237 is implicated in the regulation of hypothalamic processes associated with dopaminergic synaptic signaling, which may contribute to the formation of the behavioral/neurological phenotype and hypertensive state of ISIAH rats.

Keywords: ISIAH rat strain; behavior/neurological phenotype; hypertension; hypothalamus; long noncoding RNA.

MeSH terms

Animals
Hypertension* / genetics
Phenotype
RNA, Long Noncoding* / genetics
Rats
Stress, Physiological / genetics
Vitamin A

Substances

RNA, Long Noncoding
Vitamin A

Grants and funding

The study was supported by the Russian Foundation for Basic Research (Grant No. 20-04-00119 to O.E.R.). The preparation and maintenance of the experimental animals were carried out in the Conventional Vivarium at the Institute of Cytology and Genetics SB RAS and were supported by publicly funded project No. FWNR-2022-0019. The funding body had no role in the design of the study; in the collection, analysis, and interpretation of the data; and in the writing of the manuscript.