Research Articles Long noncoding RNA lnc-TSI inhibits renal fibrogenesis by negatively regulating the TGF-{beta}/Smad3 pathway

Transforming growth factor–β (TGF-β) is a well-established central mediator of renal fibrosis, a common outcome of almost all progressive chronic kidney diseases. Here, we identified a poorly conserved and kidney-enriched long noncoding RNA in TGF-β1–stimulated human tubular epithelial cells and fibrotic kidneys, which we termed TGF-β/Smad3-interacting long noncoding RNA (lnc-TSI). Lnc-TSI was transcriptionally regulated by Smad3 and specifically inhibited TGF-β–induced Smad3 phosphorylation and downstream profibrotic gene expression. Lnc-TSI acted by binding with the MH2 domain of Smad3, blocking the interaction of Smad3 with TGF-β receptor I independent of Smad7. Delivery of human lnc-TSI into unilateral ureteral obstruction (UUO) mice, a well-established model of renal fibrosis, inhibited phosphorylation of Smad3 in the kidney and attenuated renal fibrosis. In a cohort of 58 patients with biopsy-confirmed IgA nephropathy (IgAN), lnc-TSI renal expression negatively correlated with the renal fibrosis index (r = –0.56, P
Source: Science Translational Medicine - Category: Biomedical Science Authors: Tags: Research Articles Source Type: research

Related Links:

AbstractProgressive renal fibrosis is the last phase of chronic kidney disease and results in renal failure. Micro-RNA has been demonstrated as important agent to drive organ fibrosis. However, the precise mechanisms are not fully understood. Here, we found miRNA-184 as a critical mediator to promote the renal fibrosis by targeting HIF1AN. In Vivo, miRNA-184 expression levels remarkably increased both in patients ’ serum and in unilateral ureteral obstruction kidneys, as well as induced the expression of COL1A1 and COL3A1. Furthermore, transfection of NRK49F cells with miRNA-184 mimics down-regulated HIF1AN, transfec...
Source: International Urology and Nephrology - Category: Urology & Nephrology Source Type: research
Congenital obstructive nephropathy is a major cause of chronic kidney disease in children. The contribution of changes in the identity of renal cells to the pathology of obstructive nephropathy is poorly understood. Using a partial unilateral ureteral obstruction model in genetically modified neonatal mice, we traced the fate of cells derived from the renal stroma, cap mesenchyme, ureteric bud epithelium and podocytes using Foxd1Cre , Six2Cre , HoxB7Cre and Podocyte.Cre mice respectively, crossed with double fluorescent reporter (mT/mG) mice. Persistent obstruction leads to a significant loss of tubular epithelium, rarefac...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research
Conclusions Nephrostomy tube placement was associated with pyelonephritis and AB in 44% of cases overall. Pseudomonas and Enterococcus species were the most common pathogens. Isolation of resistant organisms was mostly observed in the pyelonephritis group.
Source: Infectious Diseases in Clinical Practice - Category: Infectious Diseases Tags: Original Articles Source Type: research
Abstract Chronic kidney disease (CKD) has become a major public health problem worldwide and has a great impact on the quality of life of millions of people. Long-term obstructive uropathy is an important cause of CKD. We hypothesized diagnostic biomarkers for early stage obstructive nephropathy can be discovered by metabolomic profiling of biofluid. Unilateral ureteral occlusion (UUO) surgery was performed on rats to induce renal interstitial fibrosis. Sham-operated rats were used as controls. Plasma and urine metabolites were analyzed by UPLC-MS based metabolomic approach. Significant metabolic profiling separat...
Source: Chemico-Biological Interactions - Category: Molecular Biology Authors: Tags: Chem Biol Interact Source Type: research
CONCLUSIONS: The antifibrotic effects of tamoxifen are associated with the suppression of Src kinase function via ER-α, followed by inhibition of the PI3K/Akt and mTOR/p70S6K signaling pathways. SIGNIFICANCE: Our findings suggest that tamoxifen is a novel therapeutic option for the prevention and treatment of renal fibrosis. This article is protected by copyright. All rights reserved. PMID: 30304547 [PubMed - as supplied by publisher]
Source: Biology of the Cell - Category: Cytology Authors: Tags: Biol Cell Source Type: research
Abstract 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 strep...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research
Conclusion: MK stent is a safe and efficient minimally invasive long-term treatment option to preserve GFR in patients who develop CKD through ureteroileal anastomotic stricture. In spite of MK stent insertion and alleviation of obstruction, it was presumably inserted too late to improve renal function.Urol Int
Source: Urologia Internationalis - Category: Urology & Nephrology Source Type: research
In this study, we first demonstrated that PA ameliorates fibroblast activation and renal interstitial fibrosis. Our results indicate that PA may be useful as a potential candidate in the prevention of chronic kidney disease.
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
In conclusion, PTF treatment ameliorated renal fibrosis and helped preserve renal function in a rodent model of PUO.
Source: Pathophysiology - Category: Pathology Source Type: research
ConclusionsPAX2 directly increased expression of ADAM10, the presence of which contributed to EMT in renal tubular epithelia and hence plays an important role in renal fibrosis.
Source: International Urology and Nephrology - Category: Urology & Nephrology Source Type: research
More News: Biomedical Science | Chronic Kidney Disease | Genetics | Science | Study | Ureter and Renal Pelvis Cancer | Urology & Nephrology