scholarly journals The Role of Tyrosine Kinase Receptors in Peritoneal Fibrosis

2015 ◽  
Vol 35 (5) ◽  
pp. 497-505 ◽  
Author(s):  
Li Wang ◽  
Shougang Zhuang
Keyword(s):  
Tyrosine Kinases ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Peritoneal Fibrosis ◽  
Functional Changes ◽  
Ultrafiltration Failure ◽  
Stage Renal Disease ◽  
End Stage

Peritoneal dialysis (PD) is a modality for treatment of patients with end-stage renal disease (ESRD) that depends on the structural and functional integrity of the peritoneal membrane. However, long-term PD can lead to morphological and functional changes in the peritoneum; in particular, peritoneal fibrosis has become one of the most common complications that ultimately results in ultrafiltration failure (UFF) and discontinuation of PD. Several factors and mechanisms such as inflammation and overproduction of transforming growth factor-β1 have been implicated in the development of peritoneal fibrosis, but there is no effective therapy to prevent or delay this process. Recent studies have shown that activation of multiple receptor tyrosine kinases (RTKs) is associated with the development and progression of tissue fibrosis in various organs, and there are also reports indicating the involvement of some RTKs in peritoneal fibrosis. This review will describe the role and mechanisms of RTKs in peritoneal fibrosis and discuss the possibility of using them as therapeutic targets for prevention and treatment of this complication.

Peritoneal fibrosis and epigenetic modulation

2020 ◽  
pp. 089686082093823
Author(s):  
Yi Wang ◽  
Yingfeng Shi ◽  
Min Tao ◽  
Shougang Zhuang ◽  
Na Liu
Keyword(s):  
End Stage Renal Disease ◽  
Noncoding Rnas ◽  
Epigenetic Modifications ◽  
Common Complication ◽  
Peritoneal Fibrosis ◽  
Ultrafiltration Failure ◽  
Epigenetic Modulation ◽  
Stage Renal Disease ◽  
End Stage

Peritoneal dialysis (PD) is an effective treatment for patients with end-stage renal disease. However, peritoneal fibrosis (PF) is a common complication that ultimately leads to ultrafiltration failure and discontinuation of PD after long-term PD therapy. There is currently no effective therapy to prevent or delay this pathologic process. Recent studies have reported epigenetic modifications involved in PF, and accumulating evidence suggests that epigenetic therapies may have the potential to prevent and treat PF clinically. The major epigenetic modifications in PF include DNA methylation, histone modification, and noncoding RNAs. The mechanisms of epigenetic regulation in PF are complex, predominantly involving modification of signaling molecules, transcriptional factors, and genes. This review will describe the mechanisms of epigenetic modulation in PF and discuss the possibility of targeting them to prevent and treat this complication.

scholarly journals Transforming growth factor-β1 hyperexpression in African American end-stage renal disease patients

1998 ◽  
Vol 53 (3) ◽  
pp. 639-644 ◽  
Author(s):  
Manikkam Suthanthiran ◽  
Ashwani Khanna ◽  
David Cukran ◽  
Rohini Adhikarla ◽  
Vijay K. Sharma ◽  
...  
Keyword(s):  
African American ◽  
Growth Factor ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Stage Renal Disease ◽  
End Stage

scholarly journals High Elmo1 expression aggravates and low Elmo1 expression prevents diabetic nephropathy

2016 ◽  
Vol 113 (8) ◽  
pp. 2218-2222 ◽  
Author(s):  
Catherine K. Hathaway ◽  
Albert S. Chang ◽  
Ruriko Grant ◽  
Hyung-Suk Kim ◽  
Victoria J. Madden ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Transforming Growth Factor ◽  
Association Studies ◽  
Lipid Peroxides ◽  
Transforming Growth Factor Β1 ◽  
Genome Wide Association Studies ◽  
Diabetic Mice ◽  
Stage Renal Disease ◽  
End Stage

Human genome-wide association studies have demonstrated that polymorphisms in the engulfment and cell motility protein 1 gene (ELMO1) are strongly associated with susceptibility to diabetic nephropathy. However, proof of causation is lacking. To test whether modest changes in its expression alter the severity of the renal phenotype in diabetic mice, we have generated mice that are type 1 diabetic because they have the Ins2Akita gene, and also have genetically graded expression of Elmo1 in all tissues ranging in five steps from ∼30% to ∼200% normal. We here show that the Elmo1 hypermorphs have albuminuria, glomerulosclerosis, and changes in the ultrastructure of the glomerular basement membrane that increase in severity in parallel with the expression of Elmo 1. Progressive changes in renal mRNA expression of transforming growth factor β1 (TGFβ1), endothelin-1, and NAD(P)H oxidase 4 also occur in parallel with Elmo1, as do the plasma levels of cystatin C, lipid peroxides, and TGFβ1, and erythrocyte levels of reduced glutathione. In contrast, Akita type 1 diabetic mice with below-normal Elmo1 expression have reduced expression of these various factors and less severe diabetic complications. Remarkably, the reduced Elmo1 expression in the 30% hypomorphs almost abolishes the pathological features of diabetic nephropathy, although it does not affect the hyperglycemia caused by the Akita mutation. Thus, ELMO1 plays an important role in the development of type 1 diabetic nephropathy, and its inhibition could be a promising option for slowing or preventing progression of the condition to end-stage renal disease.

scholarly journals Blockade of Autophagy Prevents the Development and Progression of Peritoneal Fibrosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yingfeng Shi ◽  
Yan Hu ◽  
Yi Wang ◽  
Xiaoyan Ma ◽  
Lunxian Tang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Peritoneal Fibrosis ◽  
Mesenchymal Transition ◽  
Rat Models ◽  
Ultrafiltration Failure ◽  
Tgf Β1

Peritoneal fibrosis (PF) is a major cause of ultrafiltration failure in long-term peritoneal dialysis (PD) patients. Nevertheless, limited measures have been shown to be effective for the prevention and treatment of PF. Some views reveal that activation of autophagy ameliorates PF but others demonstrate that autophagy promotes PF. It is obvious that the role of autophagy in PF is controversial and further studies are needed. Here, we investigated the role of autophagy in rat models of PF and damaged cultured human peritoneal mesothelial cells (HPMCs). Autophagy was highly activated in fibrotic peritoneum from two PF rat models induced by 4.25% peritoneal dialysate fluid (PDF) and 0.1% chlorhexidine gluconate (CG). Blockade of autophagy with 3-MA effectively prevented PF in both models and reversed epithelial to mesenchymal transition (EMT) by down-regulating TGF-β/Smad3 signaling pathway and downstream nuclear transcription factors Slug and Snail. Treatment with 3-MA also inhibited activation of EGFR/ERK1/2 signaling pathway during PF. Moreover, 3-MA prominently decreased STAT3/NF-κB-mediated inflammatory response and macrophage infiltration, and prevented peritoneal angiogenesis through downregulation of β-catenin signal. In addition, TGF-β1 stimulation up-regulated autophagic activity as evidenced by the increased autophagosome in vitro. Exposure of HPMCs to TGF-β1 resulted in the induction of EMT and activation of TGF-β/Smad3, EGFR/ERK1/2 signaling pathways. Treatment with 3-MA blocked all these responses. In addition, delayed administration of 3-MA was effective in reducing EMT induced by TGF-β1. Taken together, our study indicated that autophagy might promote PF and 3-MA had anti-fibrosis effect in vivo and in vitro. These results suggest that autophagy could be a potential target on PF therapy for clinical patients with long-term PD.

Stimulation of osteoprotegerin production is responsible for osteosclerosis in mice overexpressing TPO

Blood ◽  
2003 ◽  
Vol 101 (8) ◽  
pp. 2983-2989 ◽  
Author(s):  
Hédia Chagraoui ◽  
Micheline Tulliez ◽  
Tarek Smayra ◽  
Emiko Komura ◽  
Stéphane Giraudier ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Wild Type ◽  
Myeloproliferative Syndrome ◽  
Bone Trabeculae ◽  
Deficient Mice ◽  
Tgf Β1

Abstract Myelofibrosis and osteosclerosis are prominent features arising in mice overexpressing thrombopoietin (TPO). The pivotal role of transforming growth factor β1 (TGF-β1) in the pathogenesis of myelofibrosis has been documented, but the mechanisms mediating osteosclerosis remain unclear. Here, we used mice deficient in osteoprotegerin (OPG), a secreted inhibitor of bone resorption, to determine whether osteosclerosis occurs through a deregulation of osteoclastogenesis. Marrow cells from opg-deficient mice (opg−/−) or wild-type (WT) littermates were infected with a retrovirus encoding TPO and engrafted into anopg−/− or WT background for long-term reconstitution. The 4 combinations of graft/host (WT/WT,opg−/−/opg−/−,opg−/−/WT, and WT/opg−/−) were studied. Elevation of TPO and TGF-β1 levels in plasma was similar in the 4 experimental groups and all the mice developed a similar myeloproliferative syndrome associated with severe myelofibrosis. Osteosclerosis developed in WT hosts engrafted with WT or opg−/− hematopoietic cells and was associated with increased OPG levels in plasma and decreased osteoclastogenesis. In contrast,opg−/− hosts exhibited an osteoporotic phenotype and a growth of bone trabeculae was rarely seen. These findings suggest that osteosclerosis in mice with TPO overexpression occurs predominantly via an up-regulation of OPG in host stromal cells leading to disruption of osteoclastogenesis.

scholarly journals Role of Sodium Thiosulphate in Calciphylaxis

2021 ◽  
Vol 2 (3) ◽  
Author(s):  
Meshal Qaiser ◽  
◽  
Arora Kanwardeep ◽  
Keyword(s):  
Adverse Effect ◽  
Metabolic Acidosis ◽  
End Stage Renal Disease ◽  
Rare Condition ◽  
Sodium Thiosulphate ◽  
Calcific Uremic Arteriolopathy ◽  
Stage Renal Disease ◽  
End Stage

Calciphylaxis, also known as Calcific Uremic Arteriolopathy (CUA), is a rare condition often but not exclusively seen in end stage renal disease. Current literature recommends trial of Sodium Thiosulphate (STS) in all CUA patients. The long - term use of STS is limited by the adverse effect of Anion Gap Metabolic Acidosis (AGMA) which can be managed timely to maximize the benefits of STS.

scholarly journals Sequence Variants of Peroxisome Proliferator-Activated Receptor-Gamma Gene and the Clinical Courses of Patients with End-Stage Renal Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Chia-Ter Chao ◽  
Yen-Ching Chen ◽  
Chih-Kang Chiang ◽  
Jenq-Wen Huang ◽  
Fu-Chang Hu ◽  
...  
Keyword(s):  
Mechanistic Study ◽  
Peroxisome Proliferator ◽  
Nucleotide Polymorphisms ◽  
Term Survival ◽  
Peroxisome Proliferator Activated Receptor ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

Background.PPAR-γsingle nucleotide polymorphisms (SNPs) reportedly play an important role in determining metabolic risk among diverse population. Whether PPAR-γSNPs affect the clinical courses in ESRD patients is unknown.Methods.From a multicenter cohort, we identified 698 patients with prevalent ESRD between 2002 and 2003, and other 782 healthy subjects as control. Two PPAR-γSNPs, Pro12Ala (rs1801282) and C161T (rs3856806), were genotyped and their association with ESRD was examined. Both groups were prospectively followed until 2007, and the predictability of genotypes for the long-term survival of ESRD patients was analyzed.Results.After multivariable-adjusted regression, GG genotype of Pro12Ala was significantly more likely to associate with ESRD (P<0.001) among patients with non-diabetes-related ESRD. Cox’s proportional hazard regression showed that both Pro12Ala and C161T polymorphisms were significant predictors of mortality in ESRD patients with DM (Pro12Ala: GG versus other genotypes, hazard ratio [HR] <0.01;P<0.001; for C161T, CC versus TT genotypes, HR 2.86;P<0.001; CT versus TT genotypes, HR 1.93;P<0.001).Conclusion.This is the first and largest study to evaluate PPAR-γSNPs in ESRD patients. Further mechanistic study is needed to elucidate the role of PPAR-γamong ESRD patients.

scholarly journals Immunomodulatory Effects of the Nutraceutical Garlic Derivative Allicin in the Progression of Diabetic Nephropathy

2018 ◽  
Vol 19 (10) ◽  
pp. 3107 ◽  
Author(s):  
Abraham Arellano Buendía ◽  
Montserrat Tostado González ◽  
Omegar Sánchez Reyes ◽  
Fernando García Arroyo ◽  
Raúl Argüello García ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Proinflammatory Cytokines ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
The Status ◽  
Nuclear Factor Kappa Beta ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy (DN) is presently the primary cause of chronic kidney disease and end-stage renal disease (ESRD). It has been suggested that inflammation and oxidative stress, in addition to or in concert with the metabolic changes, plays an important role in the maintenance and progression of the disease. Therefore, attenuating or blocking these mechanisms may be a therapeutic target to delay the progression of the disease. Diallyl thiosulfinate (allicin), a compound derived from garlic, inhibits free radical formation, increases glutathione synthesis and decreases the levels of proinflammatory molecules in vitro. This research aimed to assess the effect of allicin on oxidative stress and inflammation-induced diabetes. Animals were divided into control and diabetes (streptozotocin 50 mg/kg i.p.), and maintained for 30 days. After 30 days, the group of diabetic animals was subdivided into diabetes and allicin-treated diabetes (16 mg/kg/day oral gavage). The three experimental groups were maintained for another month. We analyzed the status of renal function, oxidative stress and proinflammatory cytokines. The untreated diabetic group showed hyperglycemia and increased diuresis, creatinine clearance, proteinuria, glycosuria and urinary excretion of N-acetyl-β-d-glucosaminidase (NAG), as well as increased oxidative stress and the expression of interleukin 1β (IL-1β), IL-6, nuclear factor kappa beta (NFκβ) and transforming growth factor-β1 (TGF-β1) in plasma and kidney. In contrast, the inhibitor of NFκβ (Iκβ) is decreased in the cortex. It has been demonstrated that the allicin treatment decreases hyperglycemia, polyuria, and NAG excretion. The oxidative stress and proinflammatory cytokines were also reduced by the allicin treatment. In conclusion, allicin delays the progression of diabetic nephropathy through antioxidant and anti-inflammatory mechanisms.

Understanding the Hemodynamics Involved in Ischemic Steal Syndrome of Arteriovenous Access

2019 ◽  
Vol 24 (3) ◽  
pp. 45-48
Author(s):  
Joon Ho Hong
Keyword(s):  
Significant Role ◽  
Surgical Procedures ◽  
Successful Treatment ◽  
Arteriovenous Access ◽  
Successful Outcomes ◽  
Stage Renal Disease ◽  
End Stage ◽  
Steal Syndrome

Highlights This paper elucidates the significant role retrograde steal plays in the pathogenesis of ischemia by reviewing the successful outcomes achieved by widely employed surgical procedures. These successful interventions share an important hemodynamic feature to reverse distal ischemia: namely, the conversion of straight access configuration to a loop configuration. This conversion reduces retrograde steal, thereby increasing distal pressure and flow, resulting in the successful treatment of ischemic steal syndrome. Abstract Long-term hemodialysis, the main treatment modality for patients with end-stage renal disease, requires reliable vascular access. The arteriovenous fistula is the preferred access but remains susceptible to complications, among which ischemic steal syndrome is the most serious. The pathophysiology of ischemic steal syndrome results from the diversion of arterial flow, antegrade, retrograde, or both, into the access. Although antegrade diversion alone can cause steal syndrome, retrograde diversion plays a significant role in the development of ischemia, especially in patients with distal brachial artery-based access. Recently, the role of retrograde steal was disputed, but this paper will elucidate the significant role of retrograde steal in the pathogenesis of ischemia by reviewing the successful outcomes achieved by widely employed surgical procedures. These successful interventions share an important hemodynamic feature to reverse distal ischemia: namely, the conversion of a straight access configuration to a loop configuration. This conversion reduces retrograde steal, thereby increasing distal pressure and flow, resulting in the successful treatment of ischemic steal syndrome.

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