MicroRNA-122–5p promotes renal fibrosis and injury in spontaneously hypertensive rats by targeting FOXO3

2022 ◽  
pp. 113017
Author(s):  
Ying Liu ◽  
Zhao-Jie Dong ◽  
Jia-Wei Song ◽  
Li-Rong Liang ◽  
Lan-Lan Sun ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Abstract 309: Role of Hemeoxygenase in the Reno-Protective Effects of Soluble Epoxide Hydrolase Inhibition In Diabetic Spontaneously Hypertensive Rats

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Ahmed A Elmarakby ◽  
Jessica Faulkner ◽  
Chelsey Pye ◽  
Babak Baban ◽  
Katelyn Rouch ◽  
...  
Keyword(s):  
Protective Effect ◽  
Renal Injury ◽  
Renal Fibrosis ◽  
Spontaneously Hypertensive Rats ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
Control Group ◽  
Protective Effects ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

We previously showed that inhibition of soluble epoxide hydrolase (sEH) increased epoxyeicosatrienoic acids (EETs) levels and reduced renal injury in diabetic mice and these changes were associated with induction of hemeoxygenase-1 (HO-1). The present study determines whether the inhibition of HO negates the reno-protective effect of sEH inhibition in diabetic spontaneously hypertensive rats as a model of diabetic nephropathy in which hypertension coexists with diabetes. After six weeks of induction of diabetes with streptozotocin, SHR were divided into the following groups: untreated, treated with the sEH inhibitor, trans -4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (AUCB), treated with the HO inhibitor, stannous mesoporphyrin (SnMP), and treated with both inhibitors for four more weeks; non diabetic SHR served as a control group. Although inhibition of sEH increased renal EETs/DHETEs ratio and HO-1 activity in diabetic SHR, it did not significantly alter blood pressure (plasma EETs/DHETEs ratio was 0.5± 0.1 in AUCB-treated vs. 0.1± 0.01 in untreated diabetic SHR, P<0.05). Treatment of diabetic SHR with AUCB reduced the elevation in urinary albumin and nephrin excretion (albuminuria was 6.5± 0.5 in AUCB-treated diabetic SHR vs. 9± 1.7 mg/day in untreated diabetic SHR and nephrinuria was 70±11 in AUCB-treated diabetic SHR vs. 111± 9 μg/day in untreated diabetic SHR, P<0.05) whereas co-administration of SnMP with AUCB prevented these changes (albuminuria was 10.6± 0.6 mg/day and nephrinuria was 91±11 μg/day). Immunohistochemical analysis revealed elevations in renal fibrosis and apoptosis as evidenced by increased renal TGF-β, fibronectin and annexin V expression in diabetic SHR and these changes were reduced with sEH inhibition. Co-administration of SnMP with AUCB prevented its ability to reduce renal fibrosis and apoptosis in diabetic SHR. In addition, SnMP treatment also prevented AUCB-induced decreases in renal macrophage infiltration and renal TGF-β, NFκB and MCP-1 levels in diabetic SHR. These data suggest that HO-1 induction is involved in the protective effect of sEH inhibition against diabetic renal injury.

1: Analysis of Renal Fibrosis and Weight of Spontaneously Hypertensive Rats (SHRS) Pregnant Exposed to Physical Training

2010 ◽  
Vol 55 (4) ◽  
pp. B32
Author(s):  
Débora T.R.S. Abate ◽  
Octávio B. Neto ◽  
Ana C.G. Faleiros ◽  
Rosana R.M. Corrêa ◽  
Marlene A. Reis
Keyword(s):  
Physical Training ◽  
Renal Fibrosis ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

scholarly journals Attenuating Effects of Dieckol on Hypertensive Nephropathy in Spontaneously Hypertensive Rats

2021 ◽  
Vol 22 (8) ◽  
pp. 4230
Author(s):  
Myeongjoo Son ◽  
Seyeon Oh ◽  
Junwon Choi ◽  
Ji Tae Jang ◽  
Kuk Hui Son ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Fibrosis ◽  
Spontaneously Hypertensive Rats ◽  
Interstitial Fibrosis ◽  
Mesenchymal Cell ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Hypertensive Nephropathy ◽  
Spontaneously Hypertensive ◽  
Mesenchymal Transition

Hypertension induces renal fibrosis or tubular interstitial fibrosis, which eventually results in end-stage renal disease. Epithelial-to-mesenchymal transition (EMT) is one of the underlying mechanisms of renal fibrosis. Though previous studies showed that Ecklonia cava extracts (ECE) and dieckol (DK) had inhibitory action on angiotensin (Ang) I-converting enzyme, which converts Ang I to Ang II. It is known that Ang II is involved in renal fibrosis; however, it was not evaluated whether ECE or DK attenuated hypertensive nephropathy by decreasing EMT. In this study, the effect of ECE and DK on decreasing Ang II and its down signal pathway of angiotensin type 1 receptor (AT1R)/TGFβ/SMAD, which is related with the EMT and restoring renal function in spontaneously hypertensive rats (SHRs), was investigated. Either ECE or DK significantly decreased the serum level of Ang II in the SHRs. Moreover, the renal expression of AT1R/TGFβ/SMAD was decreased by the administration of either ECE or DK. The mesenchymal cell markers in the kidney of SHRs was significantly decreased by ECE or DK. The fibrotic tissue of the kidney of SHRs was also significantly decreased by ECE or DK. The ratio of urine albumin/creatinine of SHRs was significantly decreased by ECE or DK. Overall, the results of this study indicate that ECE and DK decreased the serum levels of Ang II and expression of AT1R/TGFβ/SMAD, and then decreased the EMT and renal fibrosis in SHRs. Furthermore, the decrease in EMT and renal fibrosis could lead to the restoration of renal function. It seems that ECE or DK could be beneficial for decreasing hypertensive nephropathy by decreasing EMT and renal fibrosis.

Serum 25-hydroxyvitamin D is associated with renal fi brosis (experimental study)

2019 ◽  
Vol 23 (6) ◽  
pp. 100-107
Author(s):  
E. O. Bogdanova ◽  
G. T. Ivanova ◽  
O. V. Galkina ◽  
I. M. Zubina ◽  
O. N. Beresneva ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Renal Fibrosis ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Hydroxyvitamin D ◽  
Period 2

INTRODUCTION. Vitamin D deficiency is commonly observed in patients with chronic kidney disease (CKD) due to decreased biosynthesis of 1,25(OH)2D3 in damaged renal tubules and increased catabolism of 1,25(OH)2D3 and 25OHD3. There is a growing evidence that vitamin D deficiency may contribute to impaired kidney function. Interventional studies have shown that vitamin D and its analogs attenuate the progression of renal fibrosis in experiment, and reduce proteinuria in patients with CKD. The renoprotective effects of vitamin D go far beyond its classical role in maintaining bone and mineral metabolism, which is a result of its pleiotropic action. THE AIM: to investigate the association between 25OH-hydroxyvitamin D (25OHD) level and renal fibrosis in spontaneously hypertensive rats (SHR) with early stages of experimental CKD.MATERIAL AND METHODS. Systolic blood pressure (BP), proteinuria, albuminuria, creatinine (Cr), urea (Ur), inorganic phosphate (Pi), 25OHD in serum were measured in nephrectomized (NE) and sham operated (SO) spontaneously hypertensive rats SHR (follow-up period 2, 4 and 6 months) and SO Wistar Kyoto rats (follow-up period 2 months), morphological light-optical study of kidney tissue was performed.RESULTS. The experimental model corresponded to the initial stages of CKD (Ur: 6.64 – 13.36 mmol/L). A significant increase in the area of renal fibrosis in animals with NE correlated with an increase in blood pressure (r = 0.51, p <0.001), serum Cr (r = 0.76, p <0.001), and albuminuria (r = 0.64, p <0.001) and proteinuria (r = 0.78, p <0.001) and a decrease in the concentration of 25OHD in serum (r = -0.67, p <0.001). In multiple regression analyzes, a reliable association of fibrosis with 25OHD was maintained (β = -0.28, p = 0.012). In addition, in ROC-analysis the largest value of the area under the curve was obtained for 25OHD (AUC = 0.95) to detect interstitial fibrosis more than 10 %.CONCLUSION. 25OHD depression at the initial stages of experimental CKD and hypertension is independently associated with the development of renal fibrosis.

scholarly journals Relaxin Reverses Cardiac and Renal Fibrosis in Spontaneously Hypertensive Rats

Hypertension ◽  
2005 ◽  
Vol 46 (2) ◽  
pp. 412-418 ◽  
Author(s):  
Edna D. Lekgabe ◽  
Helen Kiriazis ◽  
Chongxin Zhao ◽  
Qi Xu ◽  
Xiao Lei Moore ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Role of haem oxygenase in the renoprotective effects of soluble epoxide hydrolase inhibition in diabetic spontaneously hypertensive rats

2013 ◽  
Vol 125 (7) ◽  
pp. 349-359 ◽  
Author(s):  
Ahmed A. Elmarakby ◽  
Jessica Faulkner ◽  
Chelsey Pye ◽  
Katelyn Rouch ◽  
Abdulmohsin Alhashim ◽  
...  
Keyword(s):  
Renal Injury ◽  
Renal Fibrosis ◽  
Spontaneously Hypertensive Rats ◽  
Epoxide Hydrolase ◽  
Transforming Growth Factor ◽  
Soluble Epoxide Hydrolase ◽  
Control Group ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Haem Oxygenase

We have shown previously that inhibition of sEH (soluble epoxide hydrolase) increased EETs (epoxyeicosatrienoic acids) levels and reduced renal injury in diabetic mice and these changes were associated with induction of HO (haem oxygenase)-1. The present study determines whether the inhibition of HO negates the renoprotective effect of sEH inhibition in diabetic SHR (spontaneously hypertensive rats). After 6 weeks of induction of diabetes with streptozotocin, SHR were divided into the following groups: untreated, treated with the sEH inhibitor t-AUCB {trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid}, treated with the HO inhibitor SnMP (stannous mesoporphyrin), and treated with both inhibitors for 4 more weeks; non-diabetic SHR served as a control group. Induction of diabetes significantly increased renal sEH expression and decreased the renal EETs/DHETEs (dihydroxyeicosatrienoic acid) ratio without affecting HO-1 activity or expression in SHR. Inhibition of sEH with t-AUCB increased the renal EETs/DHETEs ratio and HO-1 activity in diabetic SHR; however, it did not significantly alter systolic blood pressure. Treatment of diabetic SHR with t-AUCB significantly reduced the elevation in urinary albumin and nephrin excretion, whereas co-administration of the HO inhibitor SnMP with t-AUCB prevented these changes. Immunohistochemical analysis revealed elevations in renal fibrosis as indicated by increased renal TGF-β (transforming growth factor β) levels and fibronectin expression in diabetic SHR and these changes were reduced with sEH inhibition. Co-administration of SnMP with t-AUCB prevented its ability to reduce renal fibrosis in diabetic SHR. In addition, SnMP treatment also prevented t-AUCB-induced decreases in renal macrophage infiltration, IL-17 expression and MCP-1 levels in diabetic SHR. These findings suggest that HO-1 induction is involved in the protective effect of sEH inhibition against diabetic renal injury.

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