scholarly journals Distinct Gene Expression Profiles in Colonic Organoids from Normotensive and the Spontaneously Hypertensive Rats

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1523
Author(s):  
Jing Li ◽  
Elaine M. Richards ◽  
Eileen M. Handberg ◽  
Carl J. Pepine ◽  
Mohan K. Raizada

Hypertension is associated with gut bacterial dysbiosis and gut pathology in animal models and people. Butyrate-producing gut bacteria are decreased in hypertension. RNA-seq analysis of gut colonic organoids prepared from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats was used to test the hypothesis that impaired interactions between the gut microbiome and gut epithelium are involved and that these would be remediated with butyrate supplementation. Gene expressions in immune responses including antigen presentation and antiviral pathways were decreased in the gut epithelium of the SHR in organoids and confirmed in vivo; these deficits were corrected by butyrate supplementation. Deficits in gene expression driving epithelial proliferation and differentiation were also observed in SHR. These findings highlight the importance of aligned interactions of the gut microbiome and gut immune responses to blood pressure homeostasis.

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Tsuyoshi Chiba ◽  
Tatsuki Itoh ◽  
Masaki Tabuchi ◽  
Toru Nakazawa ◽  
Takao Satou

High blood levels of inflammatory biomarkers and immune cells in stroke lesions have been recognized as results of stroke. However, recent studies have suggested that inflammation occurs prior to stroke onset. In this study, we aimed to clarify the role of inflammation in stroke onset among stroke-prone spontaneously hypertensive rats (SHRSP). At 4 weeks of age (before stroke onset), the plasma level of IL-1βwas significantly higher in SHRSP (153.0±49.7 pg/ml) than in Wistar Kyoto rats (WKY) (7.7±3.4 pg/ml,P<0.001versus SHRSP) or spontaneously hypertensive rats (SHR) (28.0±9.1 pg/ml,P<0.001versus SHRSP) (n=6per strain). Stimulated IL-1βsignal was also observed in cerebrovascular endothelial cells of SHRSP. Gene expressions of IL-1β, IL-1 receptors, caspase-1, and downstream genes (MCP-1 and ICAM-1), which associated with immune cell recruitment, were significantly greater in SHRSP than in WKY or SHR, coincident with greater NFκB protein levels in SHRSP compared to WKY or SHR. In addition, continuous administration of IL-1β(2 μg/day) using an osmotic pump slightly increased the incidence of stroke in SHR (P=0.046) and significantly accelerated the onset of stroke in SHRSP (P=0.006) compared to each control (n=10per group). These results suggest that a stimulated IL-1βsignal might be a cause of stroke onset when concomitant with severe hypertension.


Planta Medica ◽  
2017 ◽  
Vol 84 (05) ◽  
pp. 296-303 ◽  
Author(s):  
Xiaojiang Qin ◽  
Xiaomin Hou ◽  
Kun Zhang ◽  
Qingshan Li

AbstractFarrerol, a typical natural flavanone and major active component in Rhododendron dauricum var. ciliatum, has been shown to possess vasoactive ability in vitro. The aim of this study was to investigate its effect on aorta gene expression in spontaneously hypertensive rats. Twelve-week-old male normotensive Wistar Kyoto rats and spontaneously hypertensive rats were treated with orally administered farrerol (50 mg/kg body weight) for 8 wk before they were sacrificed. We found that aorta samples showed 444 upregulated genes in control spontaneously hypertensive rats compared with the control Wistar Kyoto rats. Administration of farrerol in spontaneously hypertensive rats increased the expression of 2329 genes in the aorta compared with the control spontaneously hypertensive rats. Gene expression profiles performed on the aorta revealed that farrerol induced changes in vascular smooth muscle contraction, mitogen-activated protein kinase signaling pathway, regulation of actin cytoskeleton, vascular endothelial growth factor signaling pathway, calcium signaling pathway, and renin angiotensin system. Furthermore, 10 genes involved in the pathway of vascular smooth muscle contraction were verified using real-time polymerase chain reaction technique, and several novel potential target genes for the farrerol treatment of hypertension were identified. The findings of this study lend support to the potential use of farrerol as a novel therapeutic and antihypertensive candidate drug to prevent the development of hypertension.


2005 ◽  
Vol 289 (3) ◽  
pp. F552-F561 ◽  
Author(s):  
J. M. Seubert ◽  
F. Xu ◽  
J. P. Graves ◽  
J. B. Collins ◽  
S. O. Sieber ◽  
...  

Development of hypertension stems from both environmental and genetic factors wherein the kidney plays a central role. Spontaneously hypertensive rats (SHR) and the nonhypertensive Wistar-Kyoto (WKY) controls are widely used as a model for studying hypertension. The present study examined the renal gene expression profiles between SHR and WKY at a prehypertensive stage (3 wk of age) and hypertensive stage (9 wk of age). Additionally, age-related changes in gene expression patterns were examined from 3 to 9 wk in both WKY and SHR. Five to six individual kidney samples of the same experimental group were pooled together, and quadruplicate hybridizations were performed using the National Institute of Environmental Health Sciences Rat version 2.0 Chip, which contains ∼6,700 genes. Twenty two genes were found to be differentially expressed between SHR and WKY at 3 wk of age, and 104 genes were differentially expressed at 9 wk of age. Soluble epoxide hydrolase ( Ephx2) was found to be significantly upregulated in SHR at both time points and was the predominant outlier. Conversely, elastase 1 ( Ela1) was found to be the predominant gene downregulated in SHR at both time points. Analysis of profiles at 3 vs. 9 wk of age identified 508 differentially expressed genes in WKY rats. In contrast, only 211 genes were found to be differentially expressed during this time period in SHR. The altered gene expression patterns observed in the age-related analysis suggested significant differences in the vascular extracellular matrix system between SHR and WKY kidney. Together, our data highlight the complexity of hypertension and the numerous genes involved in and affected by this condition.


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