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

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Abstract A 56-year-old Philippine seaman without any medical history presented an obstructive and prerenal acute kidney failure near the coasts of Normandy. He was hospitalized in intensive care units because of the seriousness of kidney failure and because of impaired consciousness. Abdominal computed tomography showed a destroyed left kidney, a right hydronephrosis and ureteral strictures, which is typical of urinary tuberculosis. Koch bacillus was positive in urine sample, confirming the diagnosis. Thoracic computed tomography, brain magnetic resonance imaging revealed a tuberculosis miliary with concomitant tu...
Source: Nephrologie and Therapeutique - Category: Urology & Nephrology Authors: Tags: Nephrol Ther Source Type: research
This study aims to investigate the role of ClC-5 in renal fibrosis in unilateral ureteral occlusion (UUO) mice. C57BL/6 mice received UUO surgery followed by delivery of adeno-associated virus encoding ClC-5 cDNA (AAVClC-5). Western blotting, real-time PCR and histological analysis were used to investigate the effects of ClC-5 on renal fibrosis and underlying mechanisms. The expression of ClC-5 was significantly decreased in renal cortex of UUO mice and transforming growth factor- β1 (TGF-β1)-stimulated HK2 cells. Overexpression of ClC-5 in vivo markedly ameliorated UUO-induced renal injury and fibrosis. The incr...
Source: Human Cell - Category: Cytology Source Type: research
Publication date: Available online 24 April 2019Source: Gynecologic Oncology ReportsAuthor(s): Brooke Liang, Sara S. Lange, L. Stewart Massad, Rebecca Dick, Kathryn A. Mills, Andrea R. Hagemann, Carolyn K. McCourt, Premal H. Thaker, Katherine C. Fuh, David G. Mutch, Matthew A. Powell, Lindsay M. KurokiAbstractObjectiveTo assess the renal outcomes of gynecologic oncology patients who present with hydronephrosis and acute kidney injury (AKI), have
Source: Gynecologic Oncology Reports - Category: OBGYN Source Type: research
Sara AlMarabeh, Mohammed H. Abdulla and Ken D. O'Halloran* Department of Physiology, School of Medicine, College of Medicine and Health, University College Cork, Cork, Ireland Renal sensory nerves are important in the regulation of body fluid and electrolyte homeostasis, and blood pressure. Activation of renal mechanoreceptor afferents triggers a negative feedback reno-renal reflex that leads to the inhibition of sympathetic nervous outflow. Conversely, activation of renal chemoreceptor afferents elicits reflex sympathoexcitation. Dysregulation of reno-renal reflexes by suppression of the inhibitory refle...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Therapeutic Targeting of Fibrotic Epithelial-Mesenchymal Transition–An Outstanding Challenge Attila Fintha1, Ákos Gasparics2, László Rosivall3 and Attila Sebe3,4* 12nd Department of Pathology, Semmelweis University, Budapest, Hungary 21st Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary 3Department of Pathophysiology, International Nephrology Research and Training Center, Semmelweis University, Budapest, Hungary 4Division of Medical Biotechnology, Paul Ehrlich Institute, Langen, Germany Back in 1995, a landmark paper was published, which shaped the fi...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
In this study, mice with T-cell –specific deletion of the dominant murine AT1 receptor isoform Lck-Cre Agtraflox/flox [total knockout (TKO)] and wild-type (WT) controls were subjected to the unilateral ureteral obstruction model of kidney fibrosis.
Source: American Journal of Pathology - Category: Pathology Authors: Tags: Short communication Source Type: research
In this study, mice with T-cell-specific deletion of the dominant murine AT1 receptor isoform Lck-Cre Agtraflox/flox [total knockout (TKO)] and wild-type (WT) controls were subjected to the unilateral ureteral obstruction model of kidney fibrosis. Compared with WT controls, obstructed kidneys from TKO mice at day 14 had increased collagen 1 deposition. CD4+ T cells, CD11b+Ly6Chi myeloid cells, and mRNA levels of Th1 inflammatory cytokines are elevated in obstructed TKO kidneys, suggesting that augmented Th1 responses in the TKO mice may exaggerate renal fibrosis by driving proinflammatory macrophage differentiation. In tur...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research
In this study, we first showed that blockade of glycolysis with either Dichloroacetate (DCA) or shikonin to target different glycolytic enzymes reduced renal fibrosis in the mouse model of unilateral ureteral obstruction (UUO). Both inhibitors evidently suppressed the induction of fibronectin and collagen I in obstructed kidneys with DCA also showed inhibitory effects on collagen IV and a-smooth muscle actin (a-SMA). Histological examination also confirmed less collagen deposition in DCA treated kidneys. Both DCA and shikonin significantly inhibited renal tubular apoptosis but not interstitial apoptosis in UUO. Macrophage ...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research
ConclusionIcariin treatment protects against CKD-associated renal fibrosis via its antifibrotic and anti-inflammatory properties. Icariin may serve as a therapeutic agent in the prevention of CKD-associated renal fibrosis.Graphical Abstract
Source: Phytomedicine - Category: Drugs & Pharmacology Source Type: research
In conclusion, our data indicate the potent therapeutic of BPS in mitigating fibrosis through repairing renal microvessels and suppressing endothelial-mesenchymal transition (EndMT) progression after inhibiting inflammatory and oxidative stress effects.Key messagesBPS could improve renal recovery through anti-inflammatory and anti-oxidative pathways.BPS could mitigate fibrosis through repairing renal microvessels and suppressing endothelial-mesenchymal transition (EndMT).
Source: Journal of Molecular Medicine - Category: Molecular Biology Source Type: research
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