Regulation of Synthesis and Roles of Hyaluronan in Peritoneal Dialysis

Bowen, Timothy; Meran, Soma; Williams, Ailish; Newbury, Lucy J.; Sauter, Matthias; Sitter, Thomas

doi:10.1155/2015/427038

Cited by 3 publications

(3 citation statements)

References 124 publications

(128 reference statements)

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“…This effect was confirmed, for example, in dermal, cardiac, lung, renal, and liver fibrosis 21,29–33 . As was reviewed in our previous study, 14 with respect to the peritoneal cavity, there are just a few studies focused on the role of endogenous HA in the regulation of ECM deposition and accompanying processes, most of them concerning the disruption of peritoneal membrane homeostasis during peritoneal dialysis 50 . Raby et al reported that a higher production of HA during peritoneal dialysis contributes to inflammation and fibrosis through the action TLR2 on MCs and the phosphorylation of ERK 38 .…”

Section: Discussionmentioning

confidence: 53%

“…21,[29][30][31][32][33] As was reviewed in our previous study, 14 with respect to the peritoneal cavity, there are just a few studies focused on the role of endogenous HA in the regulation of ECM deposition and accompanying processes, most of them concerning the disruption of peritoneal membrane homeostasis during peritoneal dialysis. 50 Raby et al reported that a higher production of HA during peritoneal dialysis contributes to inflammation and fibrosis through the action TLR2 on MCs and the phosphorylation of ERK. 38 During endometriosis, which can also lead to the development of adhesions, the importance of peritoneal MC-derived HA in the adherence of endometrial cells to the mesothelial monolayer was also proven.…”

Section: Discussionmentioning

confidence: 99%

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Endogenously produced hyaluronan contributes to the regulation of peritoneal adhesion development

et al. 2023

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Peritoneal adhesions are postsurgical fibrotic complications connected to peritoneal inflammation. The exact mechanism of development is unknown; however, an important role is attributed to activated mesothelial cells (MCs) overproducing macromolecules of extracellular matrix (ECM), including hyaluronic acid (HA). It was suggested that endogenously‐produced HA contributes to the regulation of different fibrosis‐related pathologies. However, little is known about the role of altered HA production in peritoneal fibrosis. We focused on the consequences of the increased turnover of HA in the murine model of peritoneal adhesions. Changes of HA metabolism were observed in early phases of peritoneal adhesion development in vivo. To study the mechanism, human MCs MeT‐5A and murine MCs isolated from the peritoneum of healthy mice were pro‐fibrotically activated by transforming growth factor β (TGFβ), and the production of HA was attenuated by two modulators of carbohydrate metabolism, 4‐methylumbelliferone (4‐MU) and 2‐deoxyglucose (2‐DG). The attenuation of HA production was mediated by upregulation of HAS2 and downregulation of HYAL2 and connected to the lower expression of pro‐fibrotic markers, including fibronectin and α‐smooth muscle actin (αSMA). Moreover, the inclination of MCs to form fibrotic clusters was also downregulated, particularly in 2‐DG‐treated cells. The effects of 2‐DG, but not 4‐MU, were connected to changes in cellular metabolism. Importantly, the inhibition of AKT phosphorylation was observed after the use of both HA production inhibitors. In summary, we identified endogenous HA as an important regulator of peritoneal fibrosis, not just a passive player during this pathological process.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Endogenously produced hyaluronan contributes to the regulation of peritoneal adhesion development

et al. 2023

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“…Elevated HA in serum in the presence of impaired liver function is informative in predicting liver fibrosis. In recent studies on rat models and PD patients, HA has been used as a biomarker for monitoring PD progression, elevated serum HA levels have been shown to predict mortality and morbidity within 18 months in PD patients [ 51 ]. But more multi‐center and larger sample size studies should be conducted afterward to further corroborate.…”

Section: Other Novel Parametersmentioning

confidence: 99%

Associations between liver function parameters and poor clinical outcomes in peritoneal dialysis patients

et al. 2022

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Patients with end-stage renal disease (ESRD) have significantly lower survival rates compared with the general population of the same age. Peritoneal dialysis (PD) is an effective treatment for patients with ESRD, but the clinical outcome of PD patients is still not promising. The survival of PD patients is associated with various clinical factors, and exploring some valid risk predictors may be beneficial for this population. In this review, by integrating the latest research, we summarized the association of some common and novel liver function parameters (ALT, AST, ALP, GGT, serum bilirubin, pre-albumin, albumin, albumin-globulin ratio [AGR], serum ferritin, and hyaluronic acid) with clinical outcomes in PD patients. It may contribute to a better understanding of potential risk factors and help to develop strategies to prevent the disease progression.

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Increased miR-7641 Levels in Peritoneal Hyalinizing Vasculopathy in Long-Term Peritoneal Dialysis Patients

Díaz

Sandoval

Rodrigues-Díez

et al. 2020

IJMS

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Peritoneal hyalinizing vasculopathy (PHV) represents the cornerstone of long-term peritoneal dialysis (PD), and especially characterizes patients associated with encapsulating peritoneal sclerosis. However, the mechanisms of PHV development remain unknown. A cross sectional study was performed in 100 non-selected peritoneal biopsies of PD patients. Clinical data were collected and lesions were evaluated by immunohistochemistry. In selected biopsies a microRNA (miRNA)-sequencing analysis was performed. Only fifteen patients (15%) showed PHV at different degrees. PHV prevalence was significantly lower among patients using PD fluids containing low glucose degradation products (GDP) (5.9% vs. 24.5%), angiotensin converting enzyme inhibitors (ACEIs) (7.5% vs. 23.4%), statins (6.5% vs. 22.6%) or presenting residual renal function, suggesting the existence of several PHV protective factors. Peritoneal biopsies from PHV samples showed loss of endothelial markers and induction of mesenchymal proteins, associated with collagen IV accumulation and wide reduplication of the basement membrane. Moreover, co-expression of endothelial and mesenchymal markers, as well as TGF-β1/Smad3 signaling activation were found in PHV biopsies. These findings suggest that an endothelial-to-mesenchymal transition (EndMT) process was taking place. Additionally, significantly higher levels of miR-7641 were observed in severe PHV compared to non-PHV peritoneal biopsies. Peritoneal damage by GDPs induce miRNA deregulation and an EndMT process in submesothelial vessels, which could contribute to collagen IV accumulation and PHV.

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Regulation of Synthesis and Roles of Hyaluronan in Peritoneal Dialysis

Cited by 3 publications

References 124 publications

Endogenously produced hyaluronan contributes to the regulation of peritoneal adhesion development

Endogenously produced hyaluronan contributes to the regulation of peritoneal adhesion development

Associations between liver function parameters and poor clinical outcomes in peritoneal dialysis patients

Increased miR-7641 Levels in Peritoneal Hyalinizing Vasculopathy in Long-Term Peritoneal Dialysis Patients

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