Elsholtzia ciliata (Thunb.) Hylander attenuates renal inflammation and interstitial fibrosis via regulation of TGF-ß and Smad3 expression on unilateral ureteral obstruction rat model

Phytomedicine ◽  
2016 ◽  
Vol 23 (4) ◽  
pp. 331-339 ◽  
Author(s):  
Tae-Won Kim ◽  
Young-Jung Kim ◽  
Chang-Seob Seo ◽  
Hyun-Tae Kim ◽  
Se-Ra Park ◽  
...  
Keyword(s):  
Rat Model ◽  
Ureteral Obstruction ◽  
Interstitial Fibrosis ◽  
Unilateral Ureteral Obstruction ◽  
Renal Inflammation ◽  
Elsholtzia Ciliata ◽  
Smad3 Expression

Inhibition of Necroptosis Attenuates Kidney Inflammation and Interstitial Fibrosis Induced By Unilateral Ureteral Obstruction

2017 ◽  
Vol 46 (2) ◽  
pp. 131-138 ◽  
Author(s):  
Xia Xiao ◽  
Chunyang Du ◽  
Zhe Yan ◽  
Yonghong Shi ◽  
Huijun Duan ◽  
...  
Keyword(s):  
Ureteral Obstruction ◽  
Potential Role ◽  
Interstitial Fibrosis ◽  
Kidney Diseases ◽  
Specific Inhibitor ◽  
Unilateral Ureteral Obstruction ◽  
Renal Diseases ◽  
Renal Interstitial Fibrosis ◽  
Renal Inflammation ◽  
Renal Histology

Background: Inflammation plays a crucial role in renal interstitial fibrosis, the pathway of chronic kidney diseases. Necroptosis is a novel form of regulated cell death, which plays a potential role in inflammation and renal diseases. The small molecule necrostatin-1 (Nec-1) is a specific inhibitor of necroptosis. This study was aimed at determining the role of necroptosis, RIP1/RIP3/mixed lineage kinase domain-like (MLKL) signaling pathway, in renal inflammation and interstitial fibrosis related to primitive tubulointerstitial injury. It was also aimed at evaluating the effect of Nec-1 in renal fibrosis induced by unilateral ureteral obstruction (UUO). Methods: Renal histology, immunohistochemistry, western blot, and real-time polymerase chain reaction were performed using UUO C57BL/6J mice model. Moreover, we tested whether Nec-1 was renal-protective in the interstitial fibrosis kidney. Mice were exposed to UUO and injected intraperitoneal with Nec-1 or vehicle. Results: The levels of RIP1/RIP3/MLKL protein and mRNA were increased in the obstructed kidneys 7 days after UUO; this was accompanied by changes in renal pathological lesions. Renal histological examination showed lesser renal damage in Nec-1-treated UUO mice. Renal inflammation, assessed by tumor necrosis factor-α, interleukin-1β, and monocyte chemotactic protein-1 was markedly attenuated by Nec-1. Furthermore, Nec-1 treatment also significantly reduced TGF-β and α-smooth muscle actin, indicating lesser renal interstitial fibrosis. Conclusion: These findings suggest that the participation of necroptosis in UUO is partly demonstrated. And necroptosis inhibition may have a potential role in the treatment of diseases with increased inflammatory response and interstitial fibrosis in renal.

Nigella sativa extract is a potent therapeutic agent for renal inflammation, apoptosis, and oxidative stress in a rat model of unilateral ureteral obstruction

2018 ◽  
Vol 32 (11) ◽  
pp. 2290-2298 ◽  
Author(s):  
Sara Hosseinian ◽  
Alireza Ebrahimzadeh Bideskan ◽  
Mohammad Naser Shafei ◽  
Hamid Reza Sadeghnia ◽  
Mohammad Soukhtanloo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rat Model ◽  
Ureteral Obstruction ◽  
Therapeutic Agent ◽  
Nigella Sativa ◽  
Unilateral Ureteral Obstruction ◽  
Renal Inflammation ◽  
Potent Therapeutic Agent ◽  
And Oxidative Stress

scholarly journals Simvastatin attenuates renal inflammation, tubular transdifferentiation and interstitial fibrosis in rats with unilateral ureteral obstruction

2005 ◽  
Vol 20 (8) ◽  
pp. 1582-1591 ◽  
Author(s):  
José Mauro Vieira ◽  
Eduardo Mantovani ◽  
Leonardo Tavares Rodrigues ◽  
Humberto Dellê ◽  
Irene Lourdes Noronha ◽  
...  
Keyword(s):  
Ureteral Obstruction ◽  
Interstitial Fibrosis ◽  
Unilateral Ureteral Obstruction ◽  
Renal Inflammation

scholarly journals Rapamycin reduces renal hypoxia, interstitial inflammation and fibrosis in a rat model of unilateral ureteral obstruction

2014 ◽  
Vol 37 (3) ◽  
pp. 142 ◽  
Author(s):  
Chun-feng Liu ◽  
Hing Liu ◽  
Yi Fang ◽  
Su-hua Jiang ◽  
Jia-ming Zhu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Protein Expression ◽  
Rat Model ◽  
Ureteral Obstruction ◽  
Interstitial Fibrosis ◽  
Unilateral Ureteral Obstruction ◽  
Tubulointerstitial Fibrosis ◽  
Interstitial Inflammation ◽  
Mrna And Protein Expression ◽  
Tgf Β1

Purpose: The purpose of this study was to explore effects of rapamycin on renal hypoxia, interstitial inflammation and fibrosis, and the expression of transforming growth factor β1 (TGF-β1), vascular endothelial growth factor (VEGF), Flk-1 and Flt-1 in a rat model of unilateral ureteral obstruction (UUO). Methods: Male Sprague-Dawley rats (n=36) were randomly divided into three groups (n=12 per group): sham surgery, UUO and UUO plus rapamycin (0.2 mg/kg/d). Serum creatinine (Scr), blood urea nitrogen, uric acid, triglycerides, cholesterol and 24-h urine protein levels were measured. The extent of interstitial fibrosis was determined by Masson's trichrome staining. ED-1 positive macrophages, type III collagen, hypoxia, TGF-1, VEGF, Flk-1, and Flt-1 mRNA and protein expressions were detected using immunohistochemical staining, real-time PCR and Western blot. Results: UUO induced an elevation in Scr, renal hypoxia, inflammation, interstitial fibrosis, TGF-β1, VEGF, Flk-1, and Flt-1 mRNA and protein expression levels (P < 0.05). Rapamycin alleviated the UUO-induced renal hypoxia, infiltration of inflammatory cells and tubulointerstitial fibrosis (at days 3 and 7). Rapamycin also down-regulated the UUO-induced elevated expression levels of TGF-β1 and Flt-1 mRNA and protein (P < 0.05). Rapamycin decreased VEGF mRNA and protein expression at day 3, and increased Flk-1 mRNA and protein expression at day 7, compared with the UUO group (P < 0.05). Conclusion: Rapamycin shows beneficial effects by reducing UUO-induced renal hypoxia, inflammation and tubulointerstitial fibrosis.

scholarly journals Follistatin, an Activin Antagonist, Ameliorates Renal Interstitial Fibrosis in a Rat Model of Unilateral Ureteral Obstruction

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Akito Maeshima ◽  
Keiichiro Mishima ◽  
Shin Yamashita ◽  
Masao Nakasatomi ◽  
Masaaki Miya ◽  
...  
Keyword(s):  
Rat Model ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Type I Collagen ◽  
Interstitial Fibrosis ◽  
Activin A ◽  
Unilateral Ureteral Obstruction ◽  
Negative Regulator ◽  
Type I ◽  
Glomerular Mesangial Cells

Activin, a member of the TGF-βsuperfamily, regulates cell growth and differentiation in various cell types. Activin A acts as a negative regulator of renal development as well as tubular regeneration after renal injury. However, it remains unknown whether activin A is involved in renal fibrosis. To clarify this issue, we utilized a rat model of unilateral ureteral obstruction (UUO). The expression of activin A was significantly increased in the UUO kidneys compared to that in contralateral kidneys. Activin A was detected in glomerular mesangial cells and interstitial fibroblasts in normal kidneys. In UUO kidneys, activin A was abundantly expressed by interstitialα-SMA-positive myofibroblasts. Administration of recombinant follistatin, an activin antagonist, reduced the fibrotic area in the UUO kidneys. The number of proliferating cells in the interstitium, but not in the tubules, was significantly lower in the follistatin-treated kidneys. Expression ofα-SMA, deposition of type I collagen and fibronectin, and CD68-positive macrophage infiltration were significantly suppressed in the follistatin-treated kidneys. These data suggest that activin A produced by interstitial fibroblasts acts as a potent profibrotic factor during renal fibrosis. Blockade of activin A action may be a novel approach for the prevention of renal fibrosis progression.

1149 BRILLIANT BLUE G, A P2X7 ANTAGONIST, ATTENUATES RENAL INFLAMMATION AND FIBROSIS IN UNILATERAL URETERAL OBSTRUCTION IN RATS

2013 ◽  
Vol 189 (4S) ◽  
Author(s):  
José Monteiro Sad Pereira ◽  
André Luis Barreira ◽  
Alberto Schanaider ◽  
Christina Maeda Takiya ◽  
Maurilo Leite ◽  
...  
Keyword(s):  
Ureteral Obstruction ◽  
Unilateral Ureteral Obstruction ◽  
Brilliant Blue ◽  
Brilliant Blue G ◽  
Renal Inflammation

scholarly journals Fight-or-flight: murine unilateral ureteral obstruction causes extensive proximal tubular degeneration, collecting duct dilatation, and minimal fibrosis

2012 ◽  
Vol 303 (1) ◽  
pp. F120-F129 ◽  
Author(s):  
Michael S. Forbes ◽  
Barbara A. Thornhill ◽  
Jordan J. Minor ◽  
Katherine A. Gordon ◽  
Carolina I. Galarreta ◽  
...  
Keyword(s):  
Renal Disease ◽  
Ureteral Obstruction ◽  
Volume Fraction ◽  
Interstitial Fibrosis ◽  
Unilateral Ureteral Obstruction ◽  
Oxidant Injury ◽  
Superoxide Formation ◽  
Atubular Glomeruli ◽  
Proximal Tubular ◽  
Fight Or Flight

Unilateral ureteral obstruction (UUO) is the most widely used animal model of progressive renal disease. Although renal interstitial fibrosis is commonly used as an end point, recent studies reveal that obstructive injury to the glomerulotubular junction leads to the formation of atubular glomeruli. To quantitate the effects of UUO on the remainder of the nephron, renal tubular and interstitial responses were characterized in mice 7 and 14 days after UUO or sham operation under anesthesia. Fractional proximal tubular mass, cell proliferation, and cell death were measured by morphometry. Superoxide formation was identified by nitro blue tetrazolium, and oxidant injury was localized by 4-hydroxynonenol and 8-hydroxydeoxyguanosine. Fractional areas of renal vasculature, interstitial collagen, α-smooth muscle actin, and fibronectin were also measured. After 14 days of UUO, the obstructed kidney loses 19% of parenchymal mass, with a 65% reduction in proximal tubular mass. Superoxide formation is localized to proximal tubules, which undergo oxidant injury, apoptosis, necrosis, and autophagy, with widespread mitochondrial loss, resulting in tubular collapse. In contrast, mitosis and apoptosis increase in dilated collecting ducts, which remain patent through epithelial cell remodeling. Relative vascular volume fraction does not change, and interstitial matrix components do not exceed 15% of total volume fraction of the obstructed kidney. These unique proximal and distal nephron cellular responses reflect differential “fight-or-flight” responses to obstructive injury and provide earlier indexes of renal injury than do interstitial compartment responses. Therapies to prevent or retard progression of renal disease should include targeting proximal tubule injury as well as interstitial fibrosis.

scholarly journals Bone Morphogenetic Protein-2 Antagonizes Renal Interstitial Fibrosis by Promoting Catabolism of Type I Transforming Growth Factor-β Receptors

Endocrinology ◽  
2009 ◽  
Vol 150 (2) ◽  
pp. 727-740 ◽  
Author(s):  
Yu-Lin Yang ◽  
Yi-Shiuan Liu ◽  
Lea-Yea Chuang ◽  
Jinn-Yuh Guh ◽  
Tao-Chen Lee ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Ureteral Obstruction ◽  
Time Course ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Unilateral Ureteral Obstruction ◽  
Bone Morphogenetic Protein 2 ◽  
Type I ◽  
Morphogenetic Protein ◽  
Tgf Β1

TGF-β is a therapeutic target for renal fibrosis. Scientists have long sought ways to antagonize TGF-β to ameliorate diabetic nephropathy. Bone morphogenetic protein (BMP-2) is a member of the TGF-β superfamily and is highly regulated in the kidney. Thus, the role of BMP-2 was investigated in NRK-49F cells (rat fibroblasts). We showed that TGF-β1 induces an increase in fibronectin. Treatment with exogenous BMP-2 or pCMV-BMP-2 significantly reversed the TGF-β1-induced increase in fibronectin concomitant with a significant decrease in type I TGF-β receptors (TGF-β RI). Moreover, BMP-2 significantly shortened the half-life of TGF-β RI. These results are related to proteosomal activation because MG132, a proteasome inhibitor, abolished BMP-2-mediated degradation of TGF-β RI. This was confirmed because BMP-2 time course dependently enhanced the ubiquitination level of TGF-β RI. In addition, Smads would seem to be involved in the interaction of BMP-2 and TGF-β. We demonstrated that BMP-2 significantly reversed the TGF-β1-induced increase in pSmad2/3 and reversed the TGF-β1-induced decrease in inhibitory Smad7. Most importantly, Smad7 small interfering RNA abolished the BMP-2-induced decrease in TGF-β RI. We evaluated the clinical efficacy of BMP-2 using unilateral ureteral obstruction rats. BMP-2 was administered ip for 7 d. In the unilateral ureteral obstruction kidneys, interstitial fibrosis was prominent. However, treatment with BMP-2 dramatically reduced Masson’s trichrome staining (collagen) in the interstitial and tubular areas of the kidneys concomitantly with a reduction in TGF-β RI. These results suggest that BMP-2 acts as a novel fibrosis antagonizing cytokine partly by down-regulating TGF-β RI and Smads. Bone morphogenetic protein-2 can antagonize TGF-β-inducing cellular fibrosis by intervening post-receptors signaling, thus disclosing an application of therapeutical potential against fibrosis disorders.

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