Aberrant expression of long noncoding RNAs in the serum and myocardium of spontaneous hypertensive rats

Yuan-jun, WU; Zhang, Zheng; Ren, Shufan; Li, Kexin; Ning, Qilan; Jiang, Xiaoying

doi:10.1007/s11033-019-05086-x

Cited by 5 publications

(5 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…P2Y 12 and P2Y 13 receptors are highly expressed by microglia and are activated predominantly by ADP ( Zhang et al, 2014 ; Weisman et al, 2012 ). P2Y 12 receptors are essential for microglial chemotaxis and have been implicated in the microglial response to cortical injury ( Haynes et al, 2006 ; Cserép et al, 2020 ), NLRP3 inflammasome activation ( Suzuki et al, 2020 ; Wu et al, 2019 ), neuronal hyperactivity and protection ( Cserép et al, 2020 ; Eyo et al, 2014 ), and blood-brain barrier maintenance ( Lou et al, 2016 ; Bisht et al, 2021 ). While purinergic receptors have been broadly identified as markers of microglial homeostasis ( Krasemann et al, 2017 ; Weisman et al, 2012 ), mechanisms by which receptor expression may drive or maintain homeostatic microglial states remain incompletely understood.…”

Section: Introductionmentioning

confidence: 99%

TREM2 regulates purinergic receptor-mediated calcium signaling and motility in human iPSC-derived microglia

Jairaman

McQuade

Granzotto

et al. 2022

eLife

View full text Add to dashboard Cite

The membrane protein TREM2 (Triggering Receptor Expressed on Myeloid cells 2) regulates key microglial functions including phagocytosis and chemotaxis. Loss-of-function variants of TREM2 are associated with increased risk of Alzheimer's disease (AD). Because abnormalities in Ca2+ signaling have been observed in several AD models, we investigated TREM2 regulation of Ca2+ signaling in human induced pluripotent stem cell-derived microglia (iPSC-microglia) with genetic deletion of TREM2. We found that iPSC-microglia lacking TREM2 (TREM2 KO) show exaggerated Ca2+ signals in response to purinergic agonists, such as ADP, that shape microglial injury responses. This ADP hypersensitivity, driven by increased expression of P2Y12 and P2Y13 receptors, results in greater release of Ca2+ from the endoplasmic reticulum (ER) stores, which triggers sustained Ca2+ influx through Orai channels and alters cell motility in TREM2 KO microglia. Using iPSC-microglia expressing the genetically encoded Ca2+ probe, Salsa6f, we found that cytosolic Ca2+ tunes motility to a greater extent in TREM2 KO microglia. Despite showing greater overall displacement, TREM2 KO microglia exhibit reduced directional chemotaxis along ADP gradients. Accordingly, the chemotactic defect in TREM2 KO microglia was rescued by reducing cytosolic Ca2+ using a P2Y12 receptor antagonist. Our results show that loss of TREM2 confers a defect in microglial Ca2+ response to purinergic signals, suggesting a window of Ca2+ signaling for optimal microglial motility.

show abstract

Section: Introductionmentioning

confidence: 99%

TREM2 regulates purinergic receptor-mediated calcium signaling and motility in human iPSC-derived microglia

Jairaman

McQuade

Granzotto

et al. 2022

eLife

View full text Add to dashboard Cite

show abstract

“…This can be explained by the previous observation of GAS5 inhibitory effect on the proliferation and migration of vascular smooth muscle cells, for which it can serve as a potential hypertension therapeutic target [26]. Considering GAS5 as a potential biomarker for hypertension has been previously elucidated in animal models [27].…”

Section: Discussionmentioning

confidence: 93%

Dysregulation in growth arrest-specific 5 and metastasis-associated lung adenocarcinoma transcript 1 gene expression predicts diagnosis and renal fibrosis in systemic lupus erythematosus patients

El-Desoky

Shemies

El-Bahnasawy

et al. 2021

Egypt J Med Hum Genet

View full text Add to dashboard Cite

Background Biomarkers that enhance overall diagnosis and prognosis of systemic lupus erythematosus (SLE) have a growing need to be recognized. The use of long non-coding ribonucleic acids (lncRNAs) as biomarkers in this regard is still largely unexplored. This study aimed to evaluate lncRNA [metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and growth arrest-specific 5 (GAS5)] expression in SLE patients with/without nephritis. Their relation to disease activity/chronicity changes has been identified. A total of 40 SLE patients and 40 healthy controls were tested using real-time quantitative polymerase chain reaction (PCR) for expression levels of MALAT1 and GAS5. Results MALAT1 expression was aberrantly upregulated, while GAS5 was downregulated in patients with SLE versus controls. GAS5 relative expression was significantly downregulated in lupus nephritis (LN) patients compared to non-lupus nephritis (NN) patients. GAS5 was also correlated with glomerulosclerosis, interstitial fibrosis, tubular atrophy, and hypertension. Conclusion The lncRNA (GAS5 and MALAT1) may serve as diagnostic biomarkers for SLE. Moreover, GAS5 may distinguish SLE LN patients from NN patients and may predict renal fibrosis in LN patients.

show abstract

“…Expression of Tnxa-ps1 has also previously been associated with the manifestation of a hypertensive phenotype. The level of lncRNA Tnxa-ps1 (formerly known as NR024118) is remarkably higher in the myocardium of spontaneously hypertensive rats [ 52 ]. Angiotensin II reduces the lncRNA Tnxa-ps1 (NR024118) amount in rat cardiac fibroblasts [ 53 ], and this effect is mediated by angiotensin II type 1 receptor–dependent signaling [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

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

Fedoseeva

Ershov

Sidorenko

et al. 2022

Genes

View full text Add to dashboard Cite

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.

show abstract

Aberrant expression of long noncoding RNAs in the serum and myocardium of spontaneous hypertensive rats

Cited by 5 publications

References 33 publications

TREM2 regulates purinergic receptor-mediated calcium signaling and motility in human iPSC-derived microglia

TREM2 regulates purinergic receptor-mediated calcium signaling and motility in human iPSC-derived microglia

Dysregulation in growth arrest-specific 5 and metastasis-associated lung adenocarcinoma transcript 1 gene expression predicts diagnosis and renal fibrosis in systemic lupus erythematosus patients

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

Contact Info

Product

Resources

About