Mefunidone Attenuates Tubulointerstitial Fibrosis in a Rat Model of Unilateral Ureteral Obstruction

Liu, Chunyan; Mei, Wenjuan; Tang, Juan; Yuan, Qiongjing; Huang, Ling; Lu, Miaomiao; Wu, Lin; Peng, Zhangzhe; Meng, Jian; Yang, Huixiang; Shen, Hong; Lv, Ben; Hu, Gaoyun; Tao, Ling

doi:10.1371/journal.pone.0129283

Cited by 26 publications

(27 citation statements)

References 42 publications

(43 reference statements)

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“…We also investigated the accumulation of type I and III collagen, which are major components of the extracellular matrix that accumulate in renal fibrosis. The kidneys in the Control group but not Sham group exhibited a significant increase in the deposition of both types of collagen on days 7 and 14, consistent with other studies . Notably, Thalido treatment reduced the deposition of both types of collagen on days 7 and 14.…”

Section: Discussionsupporting

confidence: 90%

Involvement of cytokines in the modulation and progression of renal fibrosis induced by unilateral ureteral obstruction in C57BL/6 mice: effects of thalidomide and dexamethasone

Bersani-Amado¹,

Dantas

Damião

et al. 2015

Fundamemntal Clinical Pharma

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This study investigated the kinetics of cytokines that are involved in the development of interstitial fibrosis in mice that were subjected to UUO, the interstitial type I and III collagen deposition, and the effects of Thalido and Dexa treatment on these parameters. Inbred C57BL/6 mice were divided into the groups: Normal (not submitted surgery), Sham (sham surgery), Control (UUO treated with 0.5% carboxymethyl cellulose), Thalido (UUO treated with 5 mg/kg thalidomide), and Dexa (UUO treated with 1 mg/kg dexamethasone). The treatments began the day before surgery and were administered once daily by gavage for 1, 7, or 14 days. At the end of each treatment period, blood samples were collected for the determination of creatinine, urea, cytokines. The Control group exhibited a increase in creatinine concentration compared with the Normal and Sham groups within the first 24 h after UUO, which remained high until days 7 and 14. The urea concentration was higher on days 7 and 14 in the Control group compared with the Sham group. In the Thalido and Dexa groups, a reduction of serum creatinine concentration was seen on day 14. Treatment with Dexa reduced the serum concentration of urea on day 7. The serum concentrations of cytokines (TNF-α, IL-1β, IL-6, IL-10 and IL-17) and chemokines (KC, MIG, bFGF) increased in UUO mice at all of the sampling times. The Dexa and Thalido groups exhibited alterations in the concentrations of these cytokines, suggesting the involvement of anti-inflammatory and immunomodulatory mechanisms that may have modified the fibrosis framework.

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Section: Discussionsupporting

confidence: 90%

Involvement of cytokines in the modulation and progression of renal fibrosis induced by unilateral ureteral obstruction in C57BL/6 mice: effects of thalidomide and dexamethasone

Bersani-Amado¹,

Dantas

Damião

et al. 2015

Fundamemntal Clinical Pharma

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“…Immunohistochemistry (IHC) staining was performed in paraffin sections as previously reported [29]. Slides were incubated with a primary antibody against collagen I (1:500), collagen III (1:800), CD3 (1:200), CD68 (1:200), or CBS (1:500).…”

Section: Histopathological Assessment and Immunohistochemistrymentioning

confidence: 99%

Loss of the Protein Cystathionine β-Synthase During Kidney Injury Promotes Renal Tubulointerstitial Fibrosis

Yuan¹,

Zhang²,

Xie³

et al. 2017

Kidney Blood Press Res

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Background/Aims: Renal tubulointerstitial fibrosis (TIF) is the common pathway of progressive chronic kidney disease. Inflammation has been widely accepted as the major driving force of TIF. Cystathionine β-synthase (CBS) is the first and rate-limiting enzyme in the transsulfuration pathway. CBS is considered to play protective role in liver and pulmonary fibrosis, but its role in TIF remains unknown. The purpose of this study was to investigate the potential role and mechanism of CBS in renal inflammation and TIF. Methods: Renal function, tubulointerstitium damage index score, extracellular matrix (ECM) deposition, and the expressions of collagen I, collagen III, fibronectin, CD3, CD68, IL-1β, TNF-α were measured in sham operation and unilateral ureteral obstruction (UUO) rats. Proteomics and gene array analysis were performed to screen differentially expressed molecules in the development of renal inflammation and TIF in UUO rats. The expression of CBS was detected in patients with obstructive nephropathy and UUO rats. We confirmed the expression of CBS using western blot and real-time PCR in HK-2 cells. Overexpression plasmid and siRNA were transfected specifically to study the possible function of CBS in HK-2 cells. Results: Abundant expression of CBS, localized in renal tubular epithelial cells, was revealed in human and rat renal tissue, which correlated negatively with the progression of fibrotic disease. Expression of CBS was dramatically decreased in the obstructed kidney from UUO rats as compared with the sham group (SHM). In addition, knocking down CBS exacerbated extracellular matrix (ECM) deposition, whereas CBS overexpression attenuated TGF-β1-induced ECM deposition in vitro. Inflammatory and chemotactic factors were also increased in CBS knockdown HK-2 cells stimulated by IL-1β.

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“…To repair and regenerate tubular function after acute renal disease, HGF is a key protein [36,37,39,40] which is not only considered as an endogenous anti-fibrotic factor, but also as therapeutic element that blocks renal tissue fibrosis and repair dysfunction [44]. In addition, HGF prevents accumulation of collagen in renal fibrosis [45,46]. Fig.…”

Section: Targeted Hgf Delivery To Renal Lesion Of Uuo Rat By Cba-psgtmentioning

confidence: 99%

A high affinity kidney targeting by chitobionic acid-conjugated polysorbitol gene transporter alleviates unilateral ureteral obstruction in rats

et al. 2016

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Mefunidone Attenuates Tubulointerstitial Fibrosis in a Rat Model of Unilateral Ureteral Obstruction

Cited by 26 publications

References 42 publications

Involvement of cytokines in the modulation and progression of renal fibrosis induced by unilateral ureteral obstruction in C57BL/6 mice: effects of thalidomide and dexamethasone

Involvement of cytokines in the modulation and progression of renal fibrosis induced by unilateral ureteral obstruction in C57BL/6 mice: effects of thalidomide and dexamethasone

Loss of the Protein Cystathionine β-Synthase During Kidney Injury Promotes Renal Tubulointerstitial Fibrosis

A high affinity kidney targeting by chitobionic acid-conjugated polysorbitol gene transporter alleviates unilateral ureteral obstruction in rats

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