Inflammation in Salt-Sensitive Hypertension and Renal Damage

Lu, Xiaohan; Crowley, Steven D.

doi:10.1007/s11906-018-0903-x

Cited by 62 publications

(45 citation statements)

References 99 publications

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“…In addition, recent studies strongly suggest the corelation between renal inflammation and hypertension [37, 38]. In this study, the mRNA level of TNF α elevated by NaCl was decreased with 6- gingerol treatment, and the regulation of TNF α by 6-gingerol was PPAR δ -dependent.…”

Section: Discussionsupporting

confidence: 58%

6-Gingerol Normalizes the Expression of Biomarkers Related to Hypertension via PPARδ in HUVECs, HEK293, and Differentiated 3T3-L1 Cells

et al. 2018

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Hypertension is a disease with a high prevalence and high mortality rates worldwide. In addition, various factors, such as genetic predisposition, lifestyle factors, and the abnormality of organs related to blood pressure, are involved in the development of hypertension. However, at present, there are few available drugs for hypertension that do not induce side effects. Although the therapeutic effects of ginger on hypertension are well established, the precise mechanism has not been elucidated. Therefore, this study was designed to evaluate the antihypertensive mechanism of 6-gingerol, one of the main ingredients of ginger, and to assist in the development of new drugs for hypertension without side effects. The antihypertensive effects and mechanism of 6-gingerol were identified through reverse transcription polymerase chain reaction (RT-PCR), western blotting, and immunocytochemical staining for biomarkers involved in hypertension in human umbilical vein endothelial cells (HUVECs), human embryonal kidney cells (HEK293 cells), and mouse preadipocytes (3T3-L1 cells). The lipid accumulation in differentiated 3T3-L1 cells was evaluated by using Oil Red O staining. 6- Gingerol increased the level of phosphorylated endothelial nitric oxide synthase (eNOS) protein but decreased that of vascular cell adhesion protein 1 (VCAM1) and tumor necrosis factor alpha (TNFα) in HUVECs. In HEK293 cells, the expression of the epithelial sodium channel (ENaC) protein was reduced by 6-gingerol. Lipid accumulation was attenuated by 6-gingerol treatment in differentiated 3T3-L1 cells. These effects were regulated via peroxisome proliferator-activated receptor delta (PPARδ). 6-Gingerol ameliorated the expression of biomarkers involved in the development of hypertension through PPARδ in HUVECs, HEK293, and differentiated 3T3-L1 cells.

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Section: Discussionsupporting

confidence: 58%

6-Gingerol Normalizes the Expression of Biomarkers Related to Hypertension via PPARδ in HUVECs, HEK293, and Differentiated 3T3-L1 Cells

et al. 2018

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“…Increasing evidence suggests the role of inflammation in the progression of chronic kidney disease [ 30 , 31 ]. Furthermore, salt-sensitive hypertension in human and experimental animal models has been demonstrated to be accompanied by progressive kidney damage leading to end-stage renal disease, which is associated with elevated inflammation [ 1 , 2 , 3 ].…”

Section: Discussionmentioning

confidence: 99%

“…Dietary high-salt intake does not only increase blood pressure but also induce renal injury. Accumulating evidence indicates that inflammation in the kidney plays a key role in salt-induced renal damage, leading to end-stage renal disease [ 1 , 2 , 3 ]. N-acetyl-seryl-aspartyl-lysyl-proline, a natural tetrapeptide with anti-inflammatory properties, prevented salt-induced renal damage without affecting the blood pressure in Dahl salt-sensitive (DS) rats [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, the mechanism for the renoprotective effect of BPS is still unknown. Of note, high salt induces renal inflammation in salt-sensitive hypertensive rats [ 1 , 2 , 20 ], and PGI 2 possesses anti-inflammatory action [ 11 , 14 , 16 , 18 ]. Moreover, based upon the previous reports indicating that inflammation activates Rac1 [ 21 , 22 , 23 ], there are some possibilities that BPS inhibits salt-induced Rac1-MR activation by inflammation inhibition, resulting in the attenuation of salt-induced renal damage.…”

Section: Introductionmentioning

confidence: 99%

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PGI2 Analog Attenuates Salt-Induced Renal Injury through the Inhibition of Inflammation and Rac1-MR Activation

Hirohama

Kawarazaki

Nishimoto

et al. 2020

IJMS

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Renal inflammation is known to be involved in salt-induced renal damage, leading to end-stage renal disease. This study aims to evaluate the role of inflammation in anti-inflammatory and renoprotective effects of beraprost sodium (BPS), a prostaglandin I2 (PGI2) analog, in Dahl salt-sensitive (DS) rats. Five-week-old male DS rats were fed a normal-salt diet (0.5% NaCl), a high-salt diet (8% NaCl), or a high-salt diet plus BPS treatment for 3 weeks. BPS treatment could inhibit marked proteinuria and renal injury in salt-loaded DS rats with elevated blood pressure, accompanied by renal inflammation suppression. Notably, high salt increased renal expression of active Rac1, followed by increased Sgk1 expressions, a downstream molecule of mineralocorticoid receptor (MR) signal, indicating salt-induced activation of Rac1-MR pathway. However, BPS administration inhibited salt-induced Rac1-MR activation as well as renal inflammation and damage, suggesting that Rac1-MR pathway is involved in anti-inflammatory and renoprotective effects of PGI2. Based upon Rac1 activated by inflammation, moreover, BPS inhibited salt-induced activation of Rac1-MR pathway by renal inflammation suppression, resulting in the attenuation of renal damage in salt-loaded DS rats. Thus, BPS is efficacious for the treatment of salt-induced renal injury.

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“…Macrophages and T lymphocytes participate in hypertension target organ damage 3,5,15 . To investigate if CXCR6 mediates macrophage and T cell infiltration into the kidney, we stained kidney sections for CD3, a T lymphocyte marker, and F4/80, a macrophage marker.…”

Section: Disruption Of Cxcr6 Suppresses Infiltration Of Macrophages Amentioning

confidence: 99%

Disruption of CXCR6 Ameliorates Kidney Inflammation and Fibrosis in Deoxycorticosterone Acetate/Salt Hypertension

Jin

et al. 2020

Sci Rep

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Circulating cells have a pathogenic role in the development of hypertensive nephropathy. However, how these cells infiltrate into the kidney are not fully elucidated. In this study, we investigated the role of CXCR6 in deoxycorticosterone acetate (DOCA)/salt-induced inflammation and fibrosis of the kidney. Following uninephrectomy, wild-type and CXCR6 knockout mice were treated with DOCA/ salt for 3 weeks. Blood pressure was similar between wild-type and CXCR6 knockout mice at baseline and after treatment with DOCA/salt. Wild-type mice develop significant kidney injury, proteinuria, and kidney fibrosis after three weeks of DOCA/salt treatment. CXCR6 deficiency ameliorated kidney injury, proteinuria, and kidney fibrosis following treatment with DOCA/salt. Moreover, CXCR6 deficiency inhibited accumulation of bone marrow-derived fibroblasts and myofibroblasts in the kidney following treatment with DOCA/salt. Furthermore, CXCR6 deficiency markedly reduced the number of macrophages and T cells in the kidney after DOCA/salt treatment. In summary, our results identify a critical role of CXCR6 in the development of inflammation and fibrosis of the kidney in salt-sensitive hypertension.

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Inflammation in Salt-Sensitive Hypertension and Renal Damage

Cited by 62 publications

References 99 publications

6-Gingerol Normalizes the Expression of Biomarkers Related to Hypertension via PPARδ in HUVECs, HEK293, and Differentiated 3T3-L1 Cells

6-Gingerol Normalizes the Expression of Biomarkers Related to Hypertension via PPARδ in HUVECs, HEK293, and Differentiated 3T3-L1 Cells

PGI2 Analog Attenuates Salt-Induced Renal Injury through the Inhibition of Inflammation and Rac1-MR Activation

Disruption of CXCR6 Ameliorates Kidney Inflammation and Fibrosis in Deoxycorticosterone Acetate/Salt Hypertension

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