scholarly journals Renal interstitial sclerosis in aging: effects of enalapril and nifedipine.

1996 ◽  
Vol 7 (5) ◽  
pp. 676-680 ◽  
Author(s):  
F Inserra ◽  
L A Romano ◽  
E M de Cavanagh ◽  
L Ercole ◽  
L F Ferder ◽  
...  
Keyword(s):  
Laboratory Testing ◽  
Interstitial Fibrosis ◽  
Tap Water ◽  
Kidney Tissue ◽  
Juxtaglomerular Apparatus ◽  
Aging Effects ◽  
Water Control ◽  
Renal Interstitial Fibrosis ◽  
Ad Libitum ◽  
Actin Expression

The effects of nifedipine and enalapril on age-associated renal interstitial fibrosis were investigated in 60 CF1 female mice. Mice received 20 mg enalapril (ENAL) per L (N = 20), or 40 mg nifedipine (NIF) per L (N = 20) in their drinking water. Control (CONT) mice received tap water ad libitum. The percentages of both interstitial peritubular sclerosis (IPS) in cortex and interstitial medullary sclerosis (IMS) were determined. Kidney tissue was studied using immunological techniques and optical (OM) and electron microscopy (EM) to analyze the expression of renin. alpha-SM-actin and vimentine expression were also evaluated. The results showed that blood pressure levels in ENAL or NIF animals were not different from those of CONT. Renin expression was observed in arcuate vessels (AV) in ENAL animals, whereas no renin staining in AV was found in either NIF or CONT animals. Renin immunoreactivity in the juxtaglomerular apparatus was more intense in ENAL mice, as compared with NIF or CONT animals. Laboratory testing showed the following values: proteinuria (mg/mL): CONT 6.1 +/- 0.6, NIF 11.2 +/- 2.3, and ENAL 1.0 +/- 0.6 (P < 0.05); creatinine: CONT 1.37 +/- 0.24, NIF 0.87 +/- 0.16, and ENAL 0.63 +/- 0.1 (P < 0.01). The percentages of interstitial sclerosis were: %IPS: CONT 18.12 +/- 1.1, NIF 17.40 +/- 0.9, and ENAL 3.42 +/- 1.3 (P < 0.01); %IMS: CONT 23.41 +/- 1.5, NIF 21.80 +/- 1.9, and ENAL 6.12 +/- 1.2 (P < 0.01). Percentages of alpha-SM-actin expression were: CONT 13.10 +/- 1.9, NIF 13.80 +/- 0.2, and ENAL 1.00 +/- 0.1 (P < 0.01). Vimentine staining showed no differences among the groups. It was concluded that enalapril reduces the peritubular and medullar interstitial fibrosis, whereas nifedipine has no effect.

scholarly journals Silencing of long noncoding RNA XIST protects against renal interstitial fibrosis in diabetic nephropathy via microRNA-93-5p-mediated inhibition of CDKN1A

2019 ◽  
Vol 317 (5) ◽  
pp. F1350-F1358 ◽  
Author(s):  
Jindou Yang ◽  
Yan Shen ◽  
Xia Yang ◽  
Yanjun Long ◽  
Shuang Chen ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Molecular Mechanism ◽  
High Glucose ◽  
Noncoding Rna ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Kidney Tissue ◽  
Luciferase Reporter ◽  
Renal Interstitial Fibrosis ◽  
Endogenous Expression

Long noncoding RNAs (lncRNAs) have been reported to play an important role in diabetic nephropathy (DN). However, the molecular mechanism involved in this process remains poorly understood. Thus, the present study aimed to explore the function and molecular mechanism of dysregulated lncRNA X-inactive specific transcript (XIST) in DN. DN mouse models were established by streptozotocin treatment, and human renal tubular epithelial HK-2 cells were exposed to high glucose to produce an in vitro model. XIST was highly expressed in renal tissues of patients with DN, mice with DN, and high glucose-exposed HK-2 cells. To identify the interaction among XIST, miR-93-5p, and cyclin-dependent kinase inhibitor 1A (CDKN1A) and to analyze the functional significance of their interaction in renal interstitial fibrosis, we altered endogenous expression of XIST and miR-93-5p and CDKN1A. Dual-luciferase reporter assay results suggested that XIST was highly expressed in the kidney tissue of DN mice and high glucose-exposed HK-2 cells. XIST was identified to be a lncRNA that could bind to miR-93-5p, and CDKN1A was a target of miR-93-5p. Downregulated expression of XIST led to an increase in miR-93-5p expression, thereby decreasing CDKN1A and suppressing renal interstitial fibrosis in DN. Consistently, XIST knockdown reduced the expression of fibrosis markers (fibronectin, collagen type IV, and transforming growth factor-β1). Restoration of CDKN1A or decreasing miR-93-5p yielded a reversed effect on renal interstitial fibrosis. In conclusion, our study demonstrated that silenced XIST inducing miR-93-5p-dependent CDKN1A inhibition was beneficial for preventing renal interstitial fibrosis in DN, which may provide a future strategy to prevent the progression of DN.

Effects of Dapagliflozin on Renal Interstitial Fibrosis in Diabetic Rats through Smad3, TIMP1 and MMP24 Pathway

2021 ◽  
Vol 7 (4) ◽  
pp. 690-696
Author(s):  
Yueyao Chen ◽  
Haixiang Li ◽  
Chaoqin Chen
Keyword(s):  
Interstitial Fibrosis ◽  
Intervention Group ◽  
Kidney Tissue ◽  
Diabetic Rats ◽  
Renal Interstitial Fibrosis ◽  
Blank Group ◽  
Protein Levels ◽  
Group A ◽  
Group 3 ◽  
Group 2

Objective: This research was designed to probe into the effects of Dapagliflozin on renal interstitial fibrosis in diabetic rats through Smad3, TIMP1 and MMP24 pathway. Methods: Rats were bought to establish models, and then intervened by Dapagliflozin. Human mesangial cell lines (HMCs) stimulated by high glucose were purchased, and the Smad3, TIMP1 and MMP24 levels in rats after modeling and Dapagliflozin intervention were detected. The Smad3, TIMP1 and MMP24 protein expression in kidney tissue was examined after the rats were killed, and the expression in an intervention group (IG) and a blank group (BG) were analyzed. The cells were divided into three groups: Dapagliflozin intervention (Group 1), TGF-P1/Smad3 pathway inhibitor SIS3 intervention (Group 2) and no intervention (Group 3). The TIMP1 and MMP24 levels were assessed. Results: The Smad3 and MMP24 levels in group A were higher than those in other two groups (p < 0.05), while those of TIMP1 were lower (p < 0.05). Compared with pre-intervention, the Smad3 and MMP24 levels in groups A and B decreased (p < 0.05), while those of TIMP1 increased (p < 0.05). The Smad3 and MMP24 protein levels in groups A and B were higher than those in other two groups (p < 0.05), while those of TIMP1 was lower (p < 0.05). Compared with the BG, the Smad3 and MMP24 expression in the IG was lower (p < 0.05) and that of TIMP1 was higher (p < 0.05). The TIMP1 expression in Group 3 was lower (p < 0.05) and that of MMP24 was higher than those in Groups 1 and 2 (p < 0.05). Conclusion: Dapagliflozin can treat diabetic renal interstitial fibrosis by inhibiting TGF-P1/Smad3 signaling pathway, decreasing MMP24 and increasing TIMP1.

scholarly journals Niao Du Kang Mixture Increases the Expression of mir-129-5p to Relieve Renal Fibrosis

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yan-lin Li ◽  
Lin-na Liu ◽  
Lin Huang ◽  
Hai-wen An ◽  
Jian-lin Jian ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Interstitial Fibrosis ◽  
Cell Model ◽  
Rat Kidney ◽  
Kidney Tissue ◽  
Urine Protein ◽  
Renal Interstitial Fibrosis ◽  
Expression Levels ◽  
Qrt Pcr

Objective. To investigate the efficacy of Niao Du Kang (NDK) mixture in renal fibrosis of rats and to explore the mechanism underlying the effect of NDK on renal fibrosis. Methods. Unilateral ureteral obstruction (UUO) was used to replicate a rat renal interstitial fibrosis model. The drug-administered groups were given 20 ml/kg (NDK-H), 10 ml/kg (NDK-M), and 5 ml/kg (NDK-L) NDK mixture once a day for 21 days beginning 48 hours after surgery. The 24-hour urine protein and serum creatinine (CR) levels in the sham group rats, UUO rats, and NDK mixture-treated rats were measured after the last administration. The pathological changes of rat kidney tissue were observed by HE staining. The degree of fibrosis was observed by Masson’s staining and scored. The expression levels of TGF-β, α-SMA mRNA, and mir-129-5p in kidney were detected by qRT-PCR. HK-2 cells were treated with 5 ng/ml TGF-β to induce HK-2 cell fibrosis. The expression levels of TGF-β, α-SMA mRNA, and mir-129-5p in HK-2 cells were detected by qRT-PCR. TargetScan predicted the target gene of mir-129-5p, HK-2 cells were transfected with mir-129-5p mimic, and an overexpressed mir-129-5p HK-2 cell model was constructed. qRT-PCR was used to detect the expression of PDPK1 mRNA. Western blot was used to detect the expression of PDPK1, AKT, and p-AKT in HK-2 cells induced by TGF-β and in UUO rats. Results. NDK mixture significantly reduced the 24-hour urine protein and CR levels of UUO rats. HE staining showed that the NDK mixture group exhibited a significantly reduced degree of renal interstitial fibrosis. NDK mixture also reduced the expression of TGF-β and α-SMA, and the middle-dose group showed a better therapeutic effect. In vitro studies showed that NDK mixture-containing serum increased the expression of mir-129-5p to reduce renal fibrosis. In addition, NDK mixture increased the expression of mir-129-5p in vivo. Further studies indicated that mir-129-5p could target PDPKl to reduce its expression. The NDK-containing serum group also exhibited reduced expression of PDPK1. Conclusion. NDK mixture can significantly improve renal function and improve renal fibrosis in UUO model rats. Furthermore, NDK mixture can inhibit the expression of PDPK1 by upregulating the expression of mir-129-5p and then inhibiting the PI3K/AKT pathway to improve renal fibrosis.

scholarly journals Exploring the Effect of Dapagliflozin on Alcoholic Kidney Injury and Renal Interstitial Fibrosis in Rats Based on TIMP-1/MMP-24 Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Yundou Wu ◽  
Peijun Song ◽  
Xinke Yuan ◽  
Dayong Li
Keyword(s):  
Renal Fibrosis ◽  
Interstitial Fibrosis ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Inflammatory Factors ◽  
Control Group ◽  
Renal Interstitial Fibrosis ◽  
Alcohol Group ◽  
Losartan Group ◽  
Smad3 Expression

Objective. To establish a rat model of alcoholic kidney injury and detect the expression of TIMP-1/MMP-24 in the kidneys of rats with alcoholic kidney injury at the molecular pathological level, so as to explore the mechanism of alcohol abuse leading to kidney injury and renal interstitial fibrosis as well as the alleviation of alcohol-induced kidney injury and inhibition of renal interstitial fibrosis by dapagliflozin. Methods. 48 male rats were randomly divided into 4 groups: control group, alcohol group, alcohol + dapagliflozin group, and alcohol + losartan group, each with 12 rats. Different drugs were administered by gavage for modeling and treatment. Six days later, the rats were sacrificed, blood was collected from the heart to separate the serum, and the blood creatinine (Scr) and urea nitrogen (BUN) contents were detected biochemically. After blood collection, the kidney tissue was taken and fixed in10% neutral formalin. The expression of renal tissue inflammatory factors (CRP, IL-6, and TNF-α) and renal fibrosis indexes (LN, HA, and TGF-β1) were detected; MMP-24 and TIMP-1 in the kidney tissue of rats in different treatment groups were detected, and Smad3 expression was also detected. Results. After treatment, the general condition of the alcohol + dapagliflozin group and the alcohol + losartan group improved to different degrees. The weight first decreased and then gradually increased over time. There was no statistical difference in the weight change between the two groups; Compared with the control group, the Scr level, BUN content, renal index, inflammatory factors, and renal fibrosis indexes in the alcohol group were significantly increased ( P < 0.05 ); after 6 weeks of treatment, in the alcohol + dapagliflozin group and alcohol + losartan group, Scr level, BUN content, kidney index, inflammatory factors, and renal fibrosis indexes were significantly decreased ( P < 0.05 ); the expression of MMP-24 in the kidney tissue of the control group was upregulated, and the expression of TIMP-1 and Smad3 was downregulated; MMP-24 expression was downregulated, and TIMP-1 and Smad3 expression was significantly upregulated ( P < 0.05 ) in the rats of the alcohol group. After dapagliflozin and losartan treatment, MMP-24 expression gradually increased and TIMP-1 and Smad3 expression gradually decreased ( P < 0.05 ). Conclusion. Long-term large-scale alcohol intake can cause kidney tissue damage and fibrotic lesions. The expression of fibrotic cytokines such as TIMP-1 and Smad3 will increase, and the expression of MMP-24 will be decreased. However, dapagliflozin and losartan have certain therapeutic effects on the abovementioned lesions. The mechanism may be downregulating TIMP-1 and Smad3 and upregulating the expression of MMP-24 and other cytokines in the kidney.

Dexrazoxane Alleviated Doxorubicin-Induced Nephropathy in Rats

Pharmacology ◽  
2022 ◽  
pp. 1-10
Author(s):  
Huihui Hu ◽  
Caipeng Xie ◽  
Zeping Weng ◽  
Pei Yu ◽  
Yuqiang Wang ◽  
...  
Keyword(s):  
Renal Function ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Smooth Muscle Actin ◽  
Periodic Acid ◽  
Kidney Tissue ◽  
Tunel Staining ◽  
Protective Effects ◽  
Renal Interstitial Fibrosis ◽  
Alpha Smooth Muscle Actin

<b><i>Introduction:</i></b> Doxorubicin (DOX), an anthracycline antitumor agent, has been widely used against various solid tumors and hematological malignancies. However, the clinical application of DOX is restricted by its multiple organ toxicity including nephrotoxicity. This study investigated the protective effects and mechanisms of dexrazoxane (DZR) against DOX-induced nephropathy in rats. <b><i>Methods:</i></b> Male Sprague Dawley rats received 2.5 mg/kg DOX once a week for 5 consecutive weeks. 24-h urinary protein and renal function injury biomarkers were determined to evaluate the renal function. Histopathological changes and glomerulosclerosis were examined by hematoxylin and eosin and periodic acid-Schiff staining. The change of renal ultrastructure in the DOX-induced rats was observed by the electron microscopy. The renal apoptosis was detected by TUNEL staining and measured the protein expression of Caspase-3, Bcl-2, and Bax. Renal interstitial fibrosis was determined by Masson staining and immunohistochemistry examination. The levels of vimentin, alpha-smooth muscle actin (α-SMA), and transforming growth factor β (TGF-β) in kidney tissue were detected by Western blot. <b><i>Results:</i></b> DZR pretreatment markedly raised the survival rate and improved the renal dysfunction in DOX-treated rats. DZR ameliorated DOX-induced histopathological lesion of glomerular and tubular and apoptosis. DZR restored the oxidant/antioxidant balance via regulating the levels of MDA, SOD, and TAC. DZR reduced DOX-induced collagen IV deposition and renal interstitial fibrosis and downregulated the fibrosis-related protein expressions of vimentin, α-SMA, and TGF-β1. <b><i>Conclusion:</i></b> Our results suggest DZR exerted its protective effects against DOX-induced nephropathy through inhibition of lipid peroxidation, apoptosis, and fibrosis.

scholarly journals The Effect of Giving Dadih on Malondialdehyde Levels and Renal Interstitial Fibrosis at Aging Kidney

2020 ◽  
Vol 8 (A) ◽  
pp. 293-296
Author(s):  
Harnavi Harun ◽  
Yanwirasti Yanwirasti ◽  
Bambang Purwanto ◽  
Endang Purwati Rahayuningsih
Keyword(s):  
Interstitial Fibrosis ◽  
Kidney Tissue ◽  
Thiobarbituric Acid ◽  
Buffalo Milk ◽  
Control Group ◽  
Renal Interstitial Fibrosis ◽  
Control Group Design ◽  
Free Radical Theory ◽  
Radical Theory ◽  
Aging Kidney

BACKGROUND: The increase in the elderly poses problems in the areas of health, since it can cause aging of the physiological function of organs. It also has an impact on kidney function, which will enhance the chronic kidney disease. One of the theory that causes aging process is the free radical theory, which that accumulation of free radicals is caused by depletion of antioxidants. Therefore, exogenous antioxidants are needed and in this study author use dadih. Dadih is fermented buffalo milk, indigenous from West Sumatera-Indonesia. Peptides found in fermented milk contained antioxidant that can stimulate the formation of endogenous antioxidants and diversification of dadiah increases its effect as antioxidant. AIM: This study aims to prove the effect of dadih antioxidants on malondialdehyde (MDA) levels of kidney tissue and renal interstitial fibrosis. MATERIALS AND METHODS: An experimental study with post-test only control group design conducted to observe effect of dadih to kidney aging of Rattus norvegicus in the Laboratory of Andalas University. It used 30 R. norvegicus which were divided into three groups. Group K was a positive control (did not get dadih), Group P1 was given dadih 4.5 g once a day, and Group P2 was given dadih 4.5 g twice a day for 42 days. After that, MDA levels of kidney tissue are examined using the thiobarbituric acid reactive substances examination technique and examination of renal interstitial fibrosis which is done by histopathology with Sirius-red staining. Data were analyzed using the normality test with Shapiro–Wilk. RESULTS: The results showed that dadih can reduce levels of MDA in kidney tissue, where its decrease very significant in Group P1 (given dadih once a day) and Group P2 (given dadih twice a day) compared to the Group K (control group) 0.97 ± 0.06 pg/ml to 0.75 ± 0.03 pg/ml (p < 0.05). Group P1 and Group P2 can also reduce the renal interstitial fibrosis rank. Obtained a decrease in the average fibrosis rank from Group K to Group P1 and subsequently to Group P2 (p < 0.05). CONCLUSION: This study concluded that dadih can reduce MDA levels in kidney tissue and reduce renal interstitial fibrosis rank on aging kidney.

Alteration of N6-methyladenosine epitranscriptome profile in unilateral ureteral obstructive nephropathy

Epigenomics ◽  
2020 ◽  
Vol 12 (14) ◽  
pp. 1157-1173
Author(s):  
Xueyan Li ◽  
Xu Fan ◽  
Xiaoming Yin ◽  
Huajian Liu ◽  
Yi Yang
Keyword(s):  
Western Blot ◽  
Interstitial Fibrosis ◽  
Unilateral Ureteral Obstruction ◽  
Time Dependent ◽  
Obstructive Nephropathy ◽  
Functional Importance ◽  
Renal Interstitial Fibrosis ◽  
Quantification Method ◽  
Promising Therapeutic Target ◽  
Rna Immunoprecipitation

Aim: To reveal the alterations of N6-methyladenosine (m6A) epitranscriptome profile in kidney after unilateral ureteral obstruction in mice. Materials & methods: Total renal m6A and expressions of methyltransferases and demethylases were detected by colorimetric quantification method, real-time PCR and western blot, respectively. Methylated RNA immunoprecipitation sequencing was performed to map epitranscriptome-wide m6A profile. Results: Total m6A levels were time-dependent decreased within 1 week, with the lowest level detected at day 7. A total of 823 differentially methylated transcripts in 507 genes were identified. Specifically, demethylated mRNAs selectively acted on multiple pathways, including TGF-β and WNT. Conclusion: m6A modification has a functional importance in renal interstitial fibrosis during obstructive nephropathy and might be a promising therapeutic target.

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