共查询到20条相似文献,搜索用时 15 毫秒
1.
Chiara Trincianti Vincenzo Meleca Edoardo La Porta Maurizio Bruschi Giovanni Candiano Andrea Garbarino Xhuliana Kajana Alberto Preda Francesca Lugani Gian Marco Ghiggeri Andrea Angeletti Pasquale Esposito Enrico Verrina 《International journal of molecular sciences》2022,23(10)
Peritoneal dialysis (PD) represents the dialysis modality of choice for pediatric patients with end-stage kidney disease. Indeed, compared with hemodialysis (HD), it offers many advantages, including more flexibility, reduction of the risk of hospital-acquired infections, preservation of residual kidney function, and a better quality of life. However, despite these positive aspects, PD may be associated with several long-term complications that may impair both patient’s general health and PD adequacy. In this view, chronic inflammation, caused by different factors, has a detrimental impact on the structure and function of the peritoneal membrane, leading to sclerosis and consequent PD failure both in adults and children. Although several studies investigated the complex pathogenic pathways underlying peritoneal membrane alterations, these processes remain still to explore. Understanding these mechanisms may provide novel approaches to improve the clinical outcome of pediatric PD patients through the identification of subjects at high risk of complications and the implementation of personalized interventions. In this review, we discuss the main experimental and clinical experiences exploring the potentiality of the proteomic analysis of peritoneal fluids and extracellular vesicles as a source of novel biomarkers in pediatric peritoneal dialysis. 相似文献
2.
Juan Manuel Sacnun Robin Hoogenboom Fabian Eibensteiner Isabel J. Sobieszek Markus Unterwurzacher Anja Wagner Rebecca Herzog Klaus Kratochwill 《International journal of molecular sciences》2022,23(14)
To replace kidney function, peritoneal dialysis (PD) utilizes hyperosmotic PD fluids with specific physico-chemical properties. Their composition induces progressive damage of the peritoneum, leading to vasculopathies, decline of membrane function, and PD technique failure. Clinically used PD fluids differ in their composition but still remain bioincompatible. We mapped the molecular pathomechanisms in human endothelial cells induced by the different characteristics of widely used PD fluids by proteomics. Of 7894 identified proteins, 3871 were regulated at least by 1 and 49 by all tested PD fluids. The latter subset was enriched for cell junction-associated proteins. The different PD fluids individually perturbed proteins commonly related to cell stress, survival, and immune function pathways. Modeling two major bioincompatibility factors of PD fluids, acidosis, and glucose degradation products (GDPs) revealed distinct effects on endothelial cell function and regulation of cellular stress responses. Proteins and pathways most strongly affected were members of the oxidative stress response. Addition of the antioxidant and cytoprotective additive, alanyl-glutamine (AlaGln), to PD fluids led to upregulation of thioredoxin reductase-1, an antioxidant protein, potentially explaining the cytoprotective effect of AlaGln. In conclusion, we mapped out the molecular response of endothelial cells to PD fluids, and provided new evidence for their specific pathomechanisms, crucial for improvement of PD therapies. 相似文献
3.
Justyna Miku?a-Pietrasik Patrycja Sosińska Marcin Wierzchowski Katarzyna Piwocka Krzysztof Ksi??ek 《International journal of molecular sciences》2013,14(11):22483-22498
3,3′,4,4′,5,5′-Hexahydroxy-trans-stilbene (M8) is a synthetic resveratrol derivative, advertised as a candidate drug highly effective against numerous malignancies. Because multiple tumors prone to M8 frequently metastasize into the peritoneal cavity, this study was aimed at establishing the effect of M8 on the growth and senescence of human peritoneal mesothelial cells (HPMCs), the largest cell population within the peritoneum, actively involved in the intraperitoneal spread of cancer. The study showed that M8, used at the highest non-toxic dose of 10 μM, impairs proliferation and accelerates senescence in cultured HPMCs via an oxidative stress-dependent mechanism. At the same time, soluble factors released to the environment by HPMCs that senesced prematurely in response to M8 promoted growth of colorectal and pancreatic carcinomas in vitro. These findings indicate that M8 may indirectly—through the modification of normal (mesothelial) cells phenotype—facilitate an expansion of cancer cells, which challenges the postulated value of this stilbene in chemotherapy. 相似文献
4.
Yunmee Lho Jun-Young Do Jung-Yoon Heo A-Young Kim Sang-Woon Kim Seok-Hui Kang 《International journal of molecular sciences》2021,22(9)
We investigated the effectiveness of the transforming growth factor beta-1 (TGF-β) receptor inhibitor on the epithelial to mesenchymal transition (EMT) using human peritoneal mesothelial cells (HPMCs) and examined the effectiveness of GW788388 on the peritoneal membrane using a peritoneal fibrosis mouse model. HPMCs were treated with TGF-β with or without GW788388. Animal experiments were conducted on male C57/BL6 mice. Peritoneal fibrosis was induced by intraperitoneal injection of chlorhexidine gluconate. GW788388 was administered by once-daily oral gavage. The morphological change, cell migration, and invasion resulted from TGF-β treatment, but these changes were attenuated by cotreatment with GW788388. TGF-β-treated HPMCs decreased the level of the epithelial cell marker and increased the levels of the mesenchymal cell markers. Cotreatment with GW788388 reversed these changes. Phosphorylated Smad2 and Smad3 protein levels were stimulated with TGF-β and the change was attenuated by cotreatment with GW788388. For the peritoneal fibrosis mice, thickness and collagen deposition of parietal peritoneum was increased, but this change was attenuated by cotreatment with GW788388. GW788388, an orally available potent TGF-β receptor type 1 inhibitor, effectively attenuated TGF-β-induced EMT in HPMCs. Cotreatment with GW788388 improved peritoneal thickness and fibrosis, and recovered peritoneal membrane function in a peritoneal fibrosis mouse model. GW788388相似文献
5.
Francesca Piccapane Mario Bonomini Giuseppe Castellano Andrea Gerbino Monica Carmosino Maria Svelto Arduino Arduini Giuseppe Procino 《International journal of molecular sciences》2021,22(1)
The main reason why peritoneal dialysis (PD) still has limited use in the management of patients with end-stage renal disease (ESRD) lies in the fact that the currently used glucose-based PD solutions are not completely biocompatible and determine, over time, the degeneration of the peritoneal membrane (PM) and consequent loss of ultrafiltration (UF). Here we evaluated the biocompatibility of a novel formulation of dialytic solutions, in which a substantial amount of glucose is replaced by two osmometabolic agents, xylitol and l-carnitine. The effect of this novel formulation on cell viability, the integrity of the mesothelial barrier and secretion of pro-inflammatory cytokines was evaluated on human mesothelial cells grown on cell culture inserts and exposed to the PD solution only at the apical side, mimicking the condition of a PD dwell. The results were compared to those obtained after exposure to a panel of dialytic solutions commonly used in clinical practice. We report here compelling evidence that this novel formulation shows better performance in terms of higher cell viability, better preservation of the integrity of the mesothelial layer and reduced release of pro-inflammatory cytokines. This new formulation could represent a step forward towards obtaining PD solutions with high biocompatibility. 相似文献
6.
Min Wang Lei Ding Limin Gao Yingrui Li Qirong Shen Shiwei Guo 《International journal of molecular sciences》2016,17(8)
Aquaporins, major intrinsic proteins (MIPs) present in the plasma and intracellular membranes, facilitate the transport of small neutral molecules across cell membranes in higher plants. Recently, progress has been made in understanding the mechanisms of aquaporin subcellular localization, transport selectivity, and gating properties. Although the role of aquaporins in maintaining the plant water status has been addressed, the interactions between plant aquaporins and mineral nutrients remain largely unknown. This review highlights the roles of various aquaporin orthologues in mineral nutrient uptake and transport, as well as the regulatory effects of mineral nutrients on aquaporin expression and activity, and an integrated link between aquaporins and mineral nutrient metabolism was identified. 相似文献
7.
Valentina Masola Mario Bonomini Silvio Borrelli Lorenzo Di Liberato Luigi Vecchi Maurizio Onisto Giovanni Gambaro Roberto Palumbo Arduino Arduini 《International journal of molecular sciences》2022,23(9)
Peritoneal dialysis (PD) is an efficient renal replacement therapy for patients with end-stage renal disease. Even if it ensures an outcome equivalent to hemodialysis and a better quality of life, in the long-term, PD is associated with the development of peritoneal fibrosis and the consequents patient morbidity and PD technique failure. This unfavorable effect is mostly due to the bio-incompatibility of PD solution (mainly based on high glucose concentration). In the present review, we described the mechanisms and the signaling pathway that governs peritoneal fibrosis, epithelial to mesenchymal transition of mesothelial cells, and angiogenesis. Lastly, we summarize the present and future strategies for developing more biocompatible PD solutions. 相似文献
8.
Marcelo Ozu Juan Jos Alvear-Arias Miguel Fernandez Agustín Caviglia Antonio Pea-Pichicoi Christian Carrillo Emerson Carmona Anselmo Otero-Gonzalez Jos Antonio Garate Gabriela Amodeo Carlos Gonzalez 《International journal of molecular sciences》2022,23(20)
Aquaporins (AQPs) are small transmembrane tetrameric proteins that facilitate water, solute and gas exchange. Their presence has been extensively reported in the biological membranes of almost all living organisms. Although their discovery is much more recent than ion transport systems, different biophysical approaches have contributed to confirm that permeation through each monomer is consistent with closed and open states, introducing the term gating mechanism into the field. The study of AQPs in their native membrane or overexpressed in heterologous systems have experimentally demonstrated that water membrane permeability can be reversibly modified in response to specific modulators. For some regulation mechanisms, such as pH changes, evidence for gating is also supported by high-resolution structures of the water channel in different configurations as well as molecular dynamics simulation. Both experimental and simulation approaches sustain that the rearrangement of conserved residues contributes to occlude the cavity of the channel restricting water permeation. Interestingly, specific charged and conserved residues are present in the environment of the pore and, thus, the tetrameric structure can be subjected to alter the positions of these charges to sustain gating. Thus, is it possible to explore whether the displacement of these charges (gating current) leads to conformational changes? To our knowledge, this question has not yet been addressed at all. In this review, we intend to analyze the suitability of this proposal for the first time. 相似文献
9.
Silvio Borrelli Luca De Nicola Ilaria De Gregorio Lucio Polese Luigi Pennino Claudia Elefante Alessandro Carbone Tiziana Rappa Roberto Minutolo Carlo Garofalo 《International journal of molecular sciences》2021,22(23)
Sodium overload is common in end-stage kidney disease (ESKD) and is associated with increased cardiovascular mortality that is traditionally considered a result of extracellular volume expansion. Recently, sodium storage was detected by Na23 magnetic resonance imaging in the interstitial tissue of the skin and other tissues. This amount of sodium is osmotically active, regulated by immune cells and the lymphatic system, escapes renal control, and, more importantly, is associated with salt-sensitive hypertension. In chronic kidney disease, the interstitial sodium storage increases as the glomerular filtration rate declines and is related to cardiovascular damage, regardless of the fluid overload. This sodium accumulation in the interstitial tissues becomes more significant in ESKD, especially in older and African American patients. The possible negative effects of interstitial sodium are still under study, though a higher sodium intake might induce abnormal structural and functional changes in the peritoneal wall. Interestingly, sodium stored in the interstial tissue is not unmodifiable, since it is removable by dialysis. Nevertheless, the sodium removal by peritoneal dialysis (PD) remains challenging, and new PD solutions are desirable. In this narrative review, we carried out an update on the pathophysiological mechanisms of volume-independent sodium toxicity and possible future strategies to improve sodium removal by PD. 相似文献
10.
The performances of four commercial anion-exchange membranes in the extraction of nitrate ions from water were compared in dialysis against a concentrated sodium chloride solution. The characteristic time derived from a simplified transport model for ion dialysis appears to be a convenient quantitative criterion for a selection of the best membrane for the removal of an undesirable ion. For the nitrate removal from sulfate-containing water to make it drinkable, the Neosepta ACS anion-exchange membrane appears to be the best choice due to the fast and selective removal of nitrate obtained. 相似文献
11.
Jie Wang Zong-Pei Jiang Ning Su Jin-Jin Fan Yi-Ping Ruan Wen-Xing Peng Ya-Fang Li Xue-Qing Yu 《International journal of molecular sciences》2013,14(5):10369-10382
It has been confirmed that alternatively activated macrophages (M2) participate in tissue remodeling and fibrosis occurrence, but the effect of M2 on peritoneal fibrosis related to peritoneal dialysis (PD) hasn’t been elucidated. This study was therefore conducted to assess the association between M2 and peritoneal fibrosis related to PD. In this study, peritoneal fibrosis was induced by intraperitoneal (i.p.) injection of Lactate-4.25% dialysate (100 mL/kg) to C57BL/6J mice for 28 days, and liposome-encapsulated clodronate (LC, the specific scavenger of macrophages) was used to treat the peritoneal fibrosis mice model by i.p. injection at day 18 and day 21. All animals were sacrificed at day 29. Parietal peritonea were stained with Masson’s trichrome, and the expression of type I collagen (Col-I), fibronectin, mannose receptor (CD206), transforming growth factor beta (TGF-β), chemokine receptor 7 (CCR7), chitinase 3-like 3 (Ym-1) and arginase-1 (Arg-1) was determined by Western blotting, immunofluorescence and quantitative real-time PCR. Our results revealed that peritoneal thickness, Col-I, fibronectin, CD206, TGF-β, Ym-1 and Arg-1 were upregulated in the peritoneal fibrosis mice model, and all of these indexes were downregulated in those treated with LC. Additionally, there was no difference in the level of CCR7 between the model and treatment group. Our study indicated that peritoneal M2 played an important role in the process of peritoneal fibrosis related to PD and might be a potential target for intervention therapy of peritoneal fibrosis. 相似文献
12.
Xun-Liang Zou De-An Pei Ju-Zhen Yan Gang Xu Ping Wu 《International journal of molecular sciences》2014,15(4):6592-6608
Zinc finger protein A20 is a key negative regulator of inflammation. However, whether A20 may affect inflammation during peritoneal dialysis (PD)-associated peritonitis is still unclear. This study was aimed to investigate the effect of A20 overexpression on lipopolysaccharide (LPS)-induced inflammatory response in rat peritoneal mesothelial cells (RPMCs). Isolated and cultured RPMCs in vitro. Plasmid pGEM-T easy-A20 was transfected into RPMCs by Lipofectamine™2000. The protein expression of A20, phospho-IκBα, IκBα, TNF receptor-associated factor (TRAF) 6 and CD40 were analyzed by Western blot. The mRNA expression of TRAF6, CD40, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were determined by real time-PCR. NF-κB p65 DNA binding activity, IL-6 and TNF-α levels in cells culture supernatant were determined by ELISA. Our results revealed that RPMCs overexpression of A20 lead to significant decrease of LPS-induced IκBα phosphorylation and NF-κB DNA binding activity (all p < 0.01). In addition, A20 also attenuated the expression of TRAF6, CD40, IL-6 and TNF-α as well as levels of IL-6 and TNF-α in cells culture supernatant (all p < 0.05). However, A20 only partly inhibited CD40 expression. Our study indicated that A20 overexpression may depress the inflammatory response induced by LPS in cultured RPMCs through negatively regulated the relevant function of adaptors in LPS signaling pathway. 相似文献
13.
A numerical approach, named TransChlor, is proposed to simulate transport phenomena of various substances in concrete. This approach is a theoretical model based on finite elements and finite differences methods. The model consists of coupled nonlinear partial differential equations based on Fick's diffusion law and on kinematics equations. Simulation results from a parametrical study highlight the influence of microclimatic conditions, exposure to deicing salts and concrete cover permeability and thickness on chloride ingress in concrete. The results show that the chloride ion concentration increases quickly in concrete cover when a structure is exposed to deicing salts at a mountainous location; whereas permeability of concrete cover is an insignificant parameter when the concrete is in direct or splash water contact. 相似文献
14.
15.
Francesca Bodega Chiara Sironi Luciano Zocchi Cristina Porta 《International journal of molecular sciences》2022,23(9)
To study the friction of cell monolayers avoiding damage due to stress concentration, cells can be cultured on fibrin gels, which have a structure and viscoelasticity similar to that of the extracellular matrix. In the present research, we studied different gel compositions and surface coatings in order to identify the best conditions to measure friction in vitro. We examined the adhesion and growth behavior of mesothelial cell line MET-5A on fibrin gels with different fibrinogen concentrations (15, 20, and 25 mg/mL) and with different adhesion coatings (5 μg/mL fibronectin, 10 μg/mL fibronectin, or 10 μg/mL fibronectin + 10 μg/mL collagen). We also investigated whether different substrates influenced the coefficient of friction and the ability of cells to stick to the gel during sliding. Finally, we studied the degradation rates of gels with and without cells. All substrates tested provided a suitable environment for the adherence and proliferation of mesothelial cells, and friction measurements did not cause significant cell damage or detachment. However, in gels with a lower fibrinogen concentration, cell viability was higher and cell detachment after friction measurement was lower. Fibrinolysis was negligible in all the substrates tested. 相似文献
16.
Hao-Hsi Kao Chang-Yi Kuo Darshan Tagadur Govindaraju Kuo-Su Chen Jyh-Ping Chen 《International journal of molecular sciences》2022,23(17)
Mesothelial cells are specific epithelial cells lining the serosal cavity and internal organs. Nonetheless, few studies have explored the possibility to culture mesothelial cells in a nanostructure scaffold for tissue engineering applications. Therefore, this study aims to fabricate nanofibers from a polycaprolactone (PCL) and PCL/chitosan (CS) blend by electrospinning, and to elucidate the effect of CS on the cellular response of mesothelial cells. The results demonstrate that a PCL and PCL/CS nanofiber membrane scaffold could be prepared with a comparable fiber diameter (~300 nm) and porosity for cell culture. Blending CS with PCL influenced the mechanical properties of the scaffold due to interference of PCL crystallinity in the nanofibers. However, CS substantially improves scaffold hydrophilicity and results in a ~6-times-higher cell attachment rate in PCL/CS. The mesothelial cells maintain high viability in both nanofiber membranes, but PCL/CS provides better maintenance of cobblestone-like mesothelial morphology. From gene expression analysis and immunofluorescence staining, the incorporation of CS also results in the upregulated expression of mesothelial marker genes and the enhanced production of key mesothelial maker proteins, endorsing PCL/CS to better maintain the mesothelial phenotype. The PCL/CS scaffold was therefore chosen for the in vivo studies, which involved transplanting a cell/scaffold construct containing allograft mesothelial cells for mesothelium reconstruction in rats. In the absence of mesothelial cells, the mesothelium wound covered with PCL/CS showed an inflammatory response. In contrast, a mesothelium layer similar to native mesothelium tissue could be obtained by implanting the cell/scaffold construct, based on hematoxylin and eosin (H&E) and immunohistochemical staining. 相似文献
17.
Chia-Ning Chang Chih-Yuan Niu Ann Charis Tan Chia-Hao Chan Chun-Fan Chen Tz-Heng Chen Szu-Yuan Li Yung-Tai Chen Fan-Yu Chen Wen-Sheng Liu Chih-Ching Lin Guor-Jien Wei 《International journal of molecular sciences》2021,22(7)
Peritoneal dialysis (PD) is a treatment modality for end-stage renal disease (ESRD) patients. Dextrose is a common osmotic agent used in PD solutions and its absorption may exacerbate diabetes mellitus, a common complication of ESRD. PD solutions also contain glucose degradation products (GDPs) that may lead to encapsulating peritoneal sclerosis (EPS), a severe complication of PD. A previous study showed that far-infrared (FIR) therapy improved a patient’s gastrointestinal symptoms due to EPS. Due to limited literature on the matter, this study aims to investigate dialysate GDPs and peritoneal function in diabetic patients on PD. Thirty-one PD patients were enrolled and underwent 40 min of FIR therapy twice daily for six months. We demonstrated the effect of FIR therapy on the following: (1) decrease of methylglyoxal (p = 0.02), furfural (p = 0.005), and 5-hydroxymethylfurfural (p = 0.03), (2) increase of D/D0 glucose ratio (p = 0.03), and (3) decrease of potassium levels (p = 0.008) in both DM and non-DM patients, as well as (4) maintenance and increase of peritoneal Kt/V in DM and non-DM patients, respectively (p = 0.03). FIR therapy is a non-invasive intervention that can decrease dialysate GDPs in PD patients by improving peritoneal transport rate and solute removal clearance, while also maintaining dialysis adequacy. 相似文献
18.
Benoit R. Gauthier Diana Rubio-Contreras Juan Carlos Gmez-Rosado Luis Cristobal Capitn-Morales Abdelkrim Hmadcha Bernat Soria Christian Claude Lachaud 《International journal of molecular sciences》2022,23(11)
Mesothelial cells form the mesothelium, a simple epithelium lining the walls of serous cavities and the surface of visceral organs. Although mesothelial cells are phenotypically well characterized, their immunoregulatory properties remain largely unknown, with only two studies reporting their capacity to inhibit T cells through TGF-β and their consumption of L-arginine by arginase-1. Whether human mesothelial cells can suppress other immune cells and possess additional leukosuppressive mechanisms, remain to be addressed to better delineate their therapeutic potential for cell therapy. Herein, we generated secretomes from omental mesothelial cells (OMC) and assess their capacity to inhibit lymphocytes proliferation, suppress activated T and B cells, as well as to modify macrophage activation markers. The secretome from mesenchymal stromal cells (MSC) served as a control of immuno-suppression. Although OMC and MSC were phenotypically divergent, their cytokine secretion patterns as well as expression of inflammatory and immunomodulary genes were similar. As such, OMC- and MSC-derived secretomes (OMC-S and MSC-S) both polarized RAW 264.7 macrophages towards a M2-like anti-inflammatory phenotype and suppressed mouse and human lymphocytes proliferation. OMC-S displayed a strong ability to suppress mouse- and human-activated CD19+/CD25+ B cells as compared to MSC-S. The lymphosuppressive activity of the OMC-S could be significantly counteracted either by SB-431542, an inhibitor of TGFβ and activin signaling pathways, or with a monoclonal antibody against the TGFβ1, β2, and β3 isoforms. A strong blockade of the OMC-S-mediated lymphosuppressive activity was achieved using L-NMMA, a specific inhibitor of nitric oxide synthase (NOS). Taken together, our results suggest that OMC are potent immunomodulators. 相似文献
19.
20.
Zhenghong Li Lu Zhang Weiming He Changle Zhu Jinsong Yang Meixiao Sheng 《International journal of molecular sciences》2014,15(7):12959-12971
Inflammation and transforming growth factor-β1 (TGF-β1) contribute to the development of peritoneal fibrosis (PF), which is associated with peritoneal dialysis (PD). Astragalus membranaceus (Astragalus) has anti-inflammatory and anti-fibrotic effects in many diseases. The goal of this study was to determine the anti-fibrotic effects of Astragalus on the PF response to PD. A rat model of PD was induced using standard PD fluid, and PF was verified by HE and Masson’s staining, as well as through the expression of fibroblast surface protein (FSP) and collagen III. The expression levels of monocyte chemoattractant protein (MCP)-1, F4/80 (macrophage/monocyte marker in rat), TGF-β1 and the downstream proteins phospho-SMAD 2/3 in dialyzed peritoneal tissue treated with or without Astragalus was evaluated using immunohistochemistry analysis. Overall correlations between MCP-1 and TGF-β1 staining were analyzed using both the Spearman and Pearson methods. The results showed that Astragalus could inhibit the recruitment and activation of monocytes/macrophages, thereby reducing the production of TGF-β1 in the dialyzed peritoneal membrane. PF was also significantly decreased following treatment with Astragalus. MCP-1 expression had a strong positive correlation with TGF-β1 sensitivity, suggesting that the anti-fibrotic function of Astragalus was mediated by MCP-1 and the TGF-β1 pathway. Our results indicate that Astragalus could be a useful agent against PD-induced PF. 相似文献