Dipeptidyl peptidase 4 promotes peritoneal fibrosis and its inhibitions prevent failure of peritoneal dialysis

Li, Yi-Chen; Sung, Pei‐Hsun; Yang, Ya‐Chen; Chiang, John Y.; Yip, Hon‐Kan; Yang, Chih‐Chao

doi:10.1038/s42003-021-01652-x

Cited by 14 publications

(17 citation statements)

References 55 publications

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“…Immunohistochemical staining protocols were based on our previous study 41 . Briefly, paraffin sections were treated with 3% H 2 O 2 for 10 minutes and incubated with Immuno-Block reagent (BioSB) for 30 minutes at room temperature, followed by incubation with the primary antibody specifically against Ki67 (Abcam) and secondary antibody.…”

Section: Methodsmentioning

confidence: 99%

Melatonin and hyperbaric oxygen therapies suppress colorectal carcinogenesis through pleiotropic effects and multifaceted mechanisms

Li¹,

Chen²,

Chang³

et al. 2021

Int. J. Biol. Sci.

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Colorectal cancer (CRC) is the third most common cancer worldwide. Colorectal carcinogenesis is frequently induced by hypoxia to trigger the reprogramming of cellular metabolism and gain of malignant phenotypes. Previously, hyperbaric oxygen (HBO) therapy and melatonin have been reported to alter the hypoxic microenvironment, resulting in inhibiting cancer cell survival. Accordingly, this study tested the hypothesis whether HBO and melatonin effectively inhibited CRC carcinogenesis. In vitro results indicated that melatonin therapy significantly suppressed the malignant phenotypes, including colony formation, growth, invasion, migration and cancer stemness with dose-dependent manners in CRC cell lines through multifaceted mechanisms. Similar to in vitro study, in vivo findings further demonstrated the melatonin, HBO and combined treatments effectively promoted apoptosis (cleaved-caspase 3/ cleaved-PARP) and arrested tumor proliferation, followed by inhibiting colorectal tumorigenesis in CRC xenograft tumor model. Moreover, melatonin, HBO and combined treatments modulated multifaceted mechanisms, including decreasing HIF-1α expression, alleviating AKT activation, repressing glycolytic metabolism (HK-2/PFK1/PKM2/LDH), restraining cancer stemness pathway (TGF-β/p-Smad3/Oct4/Nanog), reducing inflammation (p-NFκB/ COX-2), diminishing immune escape (PD-L1), and reversing expression of epithelial mesenchymal transition (E-cadherin/N-cadherin/MMP9). In conclusion, melatonin and HBO therapies suppressed colorectal carcinogenesis through the pleiotropic effects and multifaceted mechanisms, suggesting melatonin and HBO treatments could be novel therapeutic strategies for CRC treatment.

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Section: Methodsmentioning

confidence: 99%

Melatonin and hyperbaric oxygen therapies suppress colorectal carcinogenesis through pleiotropic effects and multifaceted mechanisms

Li¹,

Chen²,

Chang³

et al. 2021

Int. J. Biol. Sci.

Self Cite

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“…Expression of DPP4 was increased in the thickening peritoneum of chlorhexidine gluconateinduced peritoneal fibrosis model of rats. Increased expression of DPP4 in diabetes was found to promote epithelialmesenchymal transition and peritoneal fibrosis, which could be relieved by pharmacological or genetic inactivation of DPP4 (93). Moreover, DPP4 binding to extracellular matrix proteins (such as collagen and fibronectin) and extracellular matrix degrading enzymes (such as plasminogen and streptokinase) probably contributes to cells spreading and metastasis (5,94,95).…”

Section: The Role Of Dpp4 In Fibrosismentioning

confidence: 99%

Emerging Role of Dipeptidyl Peptidase-4 in Autoimmune Disease

et al. 2022

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Dipeptidyl-peptidase IV (DPP4), originally identified as an aminopeptidase in 1960s, is an ubiquitously expressed protease presented as either a membrane-bound or soluble form. DPP4 cleaves dipeptide off from the N-terminal of its substrates, altering the bioactivity of its substrates. Subsequent studies reveal that DPP4 is also involved in various cellular processes by directly binding to a number of ligands, including adenosine deaminase, CD45, fibronectin, plasminogen, and caveolin-1. In recent years, many novel functions of DPP4, such as promoting fibrosis and mediating virus entry, have been discovered. Due to its implication in fibrotic response and immunoregulation, increasing studies are focusing on the potential role of DPP4 in inflammatory disorders. As a moonlighting protein, DPP4 possesses multiple functions in different types of cells, including both enzymatic and non-enzymatic functions. However, most of the review articles on the role of DPP4 in autoimmune disease were focused on the association between DPP4 enzymatic inhibitors and the risk of autoimmune disease. An updated comprehensive summary of DPP4’s immunoregulatory actions including both enzymatic dependent and independent functions is needed. In this article, we will review the recent advances of DPP4 in immune regulation and autoimmune rheumatic disease.

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“…High glucose content induces mesothelial cells to produce transforming growth factor-beta (TGF-β) [ 15 ]. An analysis of 19,828 diabetic patients with PD has demonstrated that exposure to glucose upregulated dipeptidyl peptidase 4 (DPP4) [ 16 ]. The upregulation of dipeptidyl peptidase 4 (DPP4) promoted mesothelial to mesenchymal transition (MMT), which refers to the transition of the mesothelial membranes to the mesenchymal cells.…”

Section: Reviewmentioning

confidence: 99%

“…This clinical observational study of PD patients has shown that DPP4 enzyme played a major role in peritoneal fibrosis and deterioration. Therefore, the use of DPP4 inhibitors can help prevent the MMT [ 16 ] and prevent peritoneal fibrosis as DPP4 inhibition holds antifibrotic effects [ 17 ].…”

Section: Reviewmentioning

confidence: 99%

A Review on Major Pathways Leading to Peritoneal Fibrosis in Patients Receiving Continuous Peritoneal Dialysis

Taheri¹,

Thiagaraj²,

Shukla³

et al. 2022

Cureus

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Peritoneal fibrosis (PF) is the most important complication of peritoneal dialysis (PD) that may arise among patients receiving continuous ambulatory peritoneal dialysis (CAPD). PF is a complex process, and many factors contribute to the formation of fibrosis. PD solutions with high glucose content, chronic inflammation, inflammatory cytokines, angiogenesis, and mesothelial to mesenchymal transition (MMT) are factors contributing to the fibrosis of the peritoneum. These factors, as well as stress-induced fibrosis, are going to be discussed further in this article.Although most experimental models are promising in preventing or delaying PD-related fibrosis, most of these recommended treatment options require further research. The lack of sufficient data from real PD patients and many inconclusive data make clinicians depend on conservative treatment. New therapeutics are indeed required for the management of patients undergoing PD to prevent the dreaded complication that may arise from continuous PD. Newer PD solutions are needed to improve survival and minimize the complication associated with PD. Recently, newer PD solutions have been shown to improve patient survival and peritoneal viability and reduce this complication that may arise as a result of continuous PD.

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Dipeptidyl peptidase 4 promotes peritoneal fibrosis and its inhibitions prevent failure of peritoneal dialysis

Cited by 14 publications

References 55 publications

Melatonin and hyperbaric oxygen therapies suppress colorectal carcinogenesis through pleiotropic effects and multifaceted mechanisms

Melatonin and hyperbaric oxygen therapies suppress colorectal carcinogenesis through pleiotropic effects and multifaceted mechanisms

Emerging Role of Dipeptidyl Peptidase-4 in Autoimmune Disease

A Review on Major Pathways Leading to Peritoneal Fibrosis in Patients Receiving Continuous Peritoneal Dialysis

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