Faculty Opinions recommendation of A novel STAT3 inhibitor, S3I-201, attenuates renal interstitial fibroblast activation and interstitial fibrosis in obstructive nephropathy.

2010 ◽  
Author(s):  
Samuel Heyman
Keyword(s):  
Interstitial Fibrosis ◽  
Obstructive Nephropathy ◽  
Fibroblast Activation

scholarly journals Inhibition of histone deacetylase activity attenuates renal fibroblast activation and interstitial fibrosis in obstructive nephropathy

2009 ◽  
Vol 297 (4) ◽  
pp. F996-F1005 ◽  
Author(s):  
Maoyin Pang ◽  
Jagan Kothapally ◽  
Haiping Mao ◽  
Evelyn Tolbert ◽  
Murugavel Ponnusamy ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Interstitial Fibrosis ◽  
Kidney Diseases ◽  
Trichostatin A ◽  
Smooth Muscle Actin ◽  
Tubular Cell ◽  
Obstructive Nephropathy ◽  
Renal Tubular Cell ◽  
Fibroblast Activation ◽  
Renal Tubular

Activation of renal interstitial fibroblasts is critically involved in the development of tubulointerstitial fibrosis in chronic kidney diseases. In this study, we investigated the effect of trichostatin A (TSA), a specific histone deacetylase (HDAC) inhibitor, on the activation of renal interstitial fibroblasts in a rat renal interstitial fibroblast line (NRK-49F) and the development of renal fibrosis in a murine model of unilateral ureteral obstruction (UUO) . α-Smooth muscle actin (α-SMA) and fibronectin, two hallmarks of fibroblast activation, were highly expressed in cultured NRK-49F cells, and their expression was inhibited in the presence of TSA. Similarly, administration of TSA suppressed the expression of α-SMA and fibronectin and attenuated the accumulation of renal interstitial fibroblasts in the kidney after the obstructive injury. Activation of renal interstitial fibroblasts was accompanied by phosphorylation of signal transducer and activator of transcription 3 (STAT3), and TSA treatment also abolished these responses. Furthermore, inhibition of the STAT3 pathway with AG490 inhibited expression of α-SMA and fibronectin in NRK-49F cells. Finally, TSA treatment inhibited tubular cell apoptosis and caspase-3 activation in the obstructive kidney. Collectively, we suggest that pharmacological HDAC inhibition may induce antifibrotic activity by inactivation of renal interstitial fibroblasts and inhibition of renal tubular cell death. STAT3 may mediate those actions of HDACs.

scholarly journals A novel STAT3 inhibitor, S3I-201, attenuates renal interstitial fibroblast activation and interstitial fibrosis in obstructive nephropathy

2010 ◽  
Vol 78 (3) ◽  
pp. 257-268 ◽  
Author(s):  
Maoyin Pang ◽  
Li Ma ◽  
Rujun Gong ◽  
Evelyn Tolbert ◽  
Haiping Mao ◽  
...  
Keyword(s):  
Interstitial Fibrosis ◽  
Obstructive Nephropathy ◽  
Fibroblast Activation

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.

Obstructive nephropathy and renal fibrosis

2002 ◽  
Vol 283 (5) ◽  
pp. F861-F875 ◽  
Author(s):  
Saulo Klahr ◽  
Jeremiah Morrissey
Keyword(s):  
Renal Disease ◽  
Renal Fibrosis ◽  
Interstitial Fibrosis ◽  
Rodent Model ◽  
Renal Diseases ◽  
Obstructive Nephropathy ◽  
Therapeutic Approaches ◽  
Cellular Events ◽  
The Impact ◽  
Made In

Interstitial fibrosis has a major role in the progression of renal diseases. Several animal models are available for the study of renal fibrosis. The models of aminonucleoside-induced nephrotic syndrome, cyclosporin nephrotoxicity, and passive Heyman nephritis are characterized by molecular and cellular events similar to those that occur in obstructive nephropathy. Additionally, inhibition of angiotensin-converting enzyme exerts salutary effects on the progression of renal fibrosis in obstructive nephropathy. Unilateral ureteral obstruction (UUO) has emerged as an important model for the study of the mechanisms of renal fibrosis and also for the evaluation of the impact of potential therapeutic approaches to ameliorate renal disease. Many quantifiable pathophysiological events occur over the span of 1 wk of UUO, making this an attractive model for study. This paper reviews some of the ongoing studies that utilized a rodent model of UUO. Some of the findings of the animal model have been compared with observations made in patients with obstructive nephropathy. Most of the evidence suggests that the rodent model of UUO is reflective of human renal disease processes.

scholarly journals Reduced angiotensinogen expression attenuates renal interstitial fibrosis in obstructive nephropathy in mice

1999 ◽  
Vol 103 (1) ◽  
pp. 39-46 ◽  
Author(s):  
Robert J. Fern ◽  
Christine M. Yesko ◽  
Barbara A. Thornhill ◽  
Hyung-Suk Kim ◽  
Oliver Smithies ◽  
...  
Keyword(s):  
Interstitial Fibrosis ◽  
Obstructive Nephropathy ◽  
Renal Interstitial Fibrosis

scholarly journals Dicer deficiency in proximal tubules exacerbates renal injury and tubulointerstitial fibrosis and upregulates Smad2/3

2018 ◽  
Vol 315 (6) ◽  
pp. F1822-F1832 ◽  
Author(s):  
Zhengwei Ma ◽  
Qingqing Wei ◽  
Ming Zhang ◽  
Jian-Kang Chen ◽  
Zheng Dong
Keyword(s):  
Kidney Disease ◽  
Renal Injury ◽  
Renal Fibrosis ◽  
Interstitial Fibrosis ◽  
Proximal Tubules ◽  
Tubulointerstitial Fibrosis ◽  
Obstructive Nephropathy ◽  
Pathological Feature ◽  
Tubular Injury

Renal fibrosis is a common pathological feature in chronic kidney disease (CKD), including diabetic kidney disease (DKD) and obstructive nephropathy. Multiple microRNAs have been implicated in the pathogenesis of both DKD and obstructive nephropathy, although the overall role of microRNAs in tubular injury and renal fibrosis in CKD is unclear. Dicer (a key RNase III enzyme for microRNA biogenesis) was specifically ablated from kidney proximal tubules in mice via the Cre-lox system to deplete micoRNAs. Proximal tubular Dicer knockout (PT- Dicer KO) mice and wild-type (WT) littermates were subjected to streptozotocin (STZ) treatment to induce DKD or unilateral ureteral obstruction (UUO) to induce obstructive nephropathy. Renal hypertrophy, renal tubular apoptosis, kidney inflammation, and tubulointerstitial fibrosis were examined. Compared with WT mice, PT- Dicer KO mice showed more severe tubular injury and renal inflammation following STZ treatment. These mice also developed higher levels of tubolointerstitial fibrosis. Meanwhile, PT- Dicer KO mice had a significantly higher Smad2/3 expression in kidneys than WT mice (at 6 mo of age) in both control and STZ-treated mice. Similarly, UUO induced more severe renal injury, inflammation, and interstitial fibrosis in PT- Dicer KO mice than WT. Although we did not detect obvious Smad2/3 expression in sham-operated mice (2–3 mo old), significantly more Smad2/3 was induced in obstructed PT- Dicer KO kidneys. These results supported a protective role of Dicer-dependent microRNA synthesis in renal injury and fibrosis development in CKD, specifically in DKD and obstructive nephropathy. Depletion of Dicer and microRNAs may upregulate Smad2/3-related signaling pathway to enhance the progression of CKD.

Silymarin Regulates Tgf-β1/Smad3 Signaling Pathway and Improves Renal Tubular Interstitial Fibrosis Caused by Obstructive Nephropathy

2021 ◽  
Vol 19 (4) ◽  
pp. 508-513
Author(s):  
Jinhao Wu ◽  
Chao Huang ◽  
Gang Kan ◽  
Hanyu Xiao ◽  
Xiaoping Zhang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Interstitial Fibrosis ◽  
Tubulointerstitial Fibrosis ◽  
Obstructive Nephropathy ◽  
Therapeutic Drugs ◽  
Renal Tubulointerstitial Fibrosis ◽  
Liver And Kidney ◽  
Renal Tubular ◽  
Antioxidant Effects ◽  
Tgf Β1

Obstructive nephropathy often leads to renal tubulointerstitial fibrosis. Understanding of the pathogenesis of renal tubulointerstitial fibrosis caused by obstructive nephropathy is crucial to the development of effective therapeutic drugs to improve the prognosis of the patients. Silymarin, a polyphenolic flavonoid extracted from plants, has been shown to exhibit antiinflammatory and antioxidant effects ameliorating liver and kidney damage. However, the effect of silymarin on renal fibrosis in obstructive nephropathy remains to be explored. In this study, we found silymarin improved interstitial fibrosis and apoptosis induced by TGF-β1 and ameliorated oxidative damage. Our data further confirmed that silymarin regulates the TGF-β1/ Smad3 signaling pathway, and therefore improves renal tubular interstitial fibrosis caused by obstructive nephropathy.

scholarly journals Ureteral obstruction as a model of renal interstitial fibrosis and obstructive nephropathy

2009 ◽  
Vol 75 (11) ◽  
pp. 1145-1152 ◽  
Author(s):  
Robert L. Chevalier ◽  
Michael S. Forbes ◽  
Barbara A. Thornhill
Keyword(s):  
Ureteral Obstruction ◽  
Interstitial Fibrosis ◽  
Obstructive Nephropathy ◽  
Renal Interstitial Fibrosis

scholarly journals Quantification of TGF-β1 mRNA along rat nephron in obstructive nephropathy

2001 ◽  
Vol 281 (3) ◽  
pp. F513-F521 ◽  
Author(s):  
Kyoichi Fukuda ◽  
Koji Yoshitomi ◽  
Taihei Yanagida ◽  
Masanori Tokumoto ◽  
Hideki Hirakata
Keyword(s):  
In Situ Hybridization ◽  
Mrna Expression ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Proximal Tubules ◽  
Obstructive Nephropathy ◽  
Renal Tubules ◽  
Rt Pcr ◽  
Tgf Β1

Unilateral ureteral obstruction (UUO) leads to interstitial fibrosis of the obstructed kidney, and transforming growth factor-β1 (TGF-β1) is thought to play an important role in this process. Although increased TGF-β1 mRNA expression in the obstructed kidney has been demonstrated, the source of the increased TGF-β1 remains to be elucidated. To determine the precise localization of TGF-β1 in the obstructed kidney, we examined TGF-β1 mRNA expression using in situ hybridization and competitive RT-PCR in rats with UUO. In situ hybridization demonstrated that TGF-β1 mRNA expression was preferentially increased in tubular epithelial cells and to a lesser degree in infiltrating macrophages in obstructed kidneys. Quantitative analysis using competitive RT-PCR in microdissected nephron segments revealed that levels of TGF-β1 mRNA in obstructed kidneys relative to control kidneys increased significantly in proximal tubules, thick ascending limbs of Henle, and distal convoluted tubules, whereas those in glomeruli and collecting ducts did not change significantly. Of the tubular segments, the proximal tubules appeared to predominantly contribute to increased TGF-β1 mRNA. Our findings suggest that renal tubules, particularly proximal tubules, are the main contributors to increased TGF-β1 mRNA expression in obstructed kidneys and to the subsequent interstitial fibrosis.

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