The Differential Effect of Apyrase Treatment and hCD39 Overexpression on Chronic Renal Fibrosis After Ischemia-Reperfusion Injury

Roberts, Veena; Campbell, Duncan J.; Lü, Bo; Chia, Joanne S. J.; Cowan, Peter J.; Dwyer, Karen M.

doi:10.1097/tp.0000000000001679

Cited by 16 publications

(14 citation statements)

References 41 publications

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“…Acute kidney injury (AKI) is a prominent risk factor for the development of CKD [8]. In recent years, ischemia-induced AKI have attracted much attention because of high rate of later renal fibrosis [9,10]. However, the related specific mechanism have not been rigorously explored.…”

Section: Introductionmentioning

confidence: 99%

TAK1 mediates apoptosis via p38 involve in ischemia-induced renal fibrosis

Zhou

Zhong

Huang

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

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Renal fibrosis is a common and characteristic symptom of chronic kidney disease (CKD). However, the molecular mechanisms of renal fibrosis remain elusive. Ischemia injury, as a major cause of AKI, deserves more attention in order to improve the knowledge of AKI-induced fibrosis. Transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) interacts directly with TGF-β, which play a critical role in the progression of fibrosis. Therefore, the present study aimed to investigate the role of TAK1 in the pathogenesis of ischemia-induced renal fibrosis. Compared with mice in the vehicle group, mice intraperitoneally injected with TAK1 inhibitor were found to have lower serum creatinine, less tubular damage and more mild fibrosis following ischemia-induced AKI. Furthermore, inhibition of TAK1 reduced p38 phosphorylation, decreased expression of Bax and caspase 3 and apoptosis cells in kidneys of mice treated with IR-induced AKI. Compared with vehicle-treated renal tubular epithelial cells, TAK1 overexpression cells were found to have a higher apoptosis and fibrosis index level and p38 phosphorylation following hypoxia/reoxygenation (H/R) treatment. Furthermore, the p38 inhibitor combined with TAK1 overexpression verified the role of TAK1/p38 signaling pathway in apoptosis and fibrosis index level of renal tubular epithelial cells treated with H/R. Thus, our results show that TAK1 plays an important role in the pathogenesis of ischemia-induced renal fibrosis and may mediate p38-regulated cell apoptosis.

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Section: Introductionmentioning

confidence: 99%

TAK1 mediates apoptosis via p38 involve in ischemia-induced renal fibrosis

Zhou

Zhong

Huang

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

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“…Lung fibrosis (Wang et al, 2009) Lentiviral depletion; rat silicosis model Activation of L-TGF-β1; production of hydroxyproline and ECM Profibrotic CD39 Chronic renal Fibrosis (Roberts et al, 2017) CD39 over-expressing transgenic mice…”

Section: Profibroticmentioning

confidence: 99%

“…However, the role of CD39 protein per se in fibrotic diseases have been studied and showed competing results. On one hand, CD39 hyperfunction caused the accumulation of extracellular ADO and facilitated the activation of ADO signaling pathway, resulting in tissue fibrosis (Roberts et al, 2017). In renal ischemia-reperfusion injury models, overexpression of CD39 in the transgenic mice showed significantly more severe renal fibrosis via upregulating ADO and stimulating profibrotic downstream pathways through interaction with adenosine A2B receptors (Roberts et al, 2017).…”

Section: Adenosine Generation Profibroticmentioning

confidence: 99%

“…On one hand, CD39 hyperfunction caused the accumulation of extracellular ADO and facilitated the activation of ADO signaling pathway, resulting in tissue fibrosis (Roberts et al, 2017). In renal ischemia-reperfusion injury models, overexpression of CD39 in the transgenic mice showed significantly more severe renal fibrosis via upregulating ADO and stimulating profibrotic downstream pathways through interaction with adenosine A2B receptors (Roberts et al, 2017). Consistently, antifibrogenic effects of CD39 depletion have been observed in bleomycin-induced skin fibrosis (Fernández et al, 2013) and cyclosporin-induced pancreatitis (Künzli et al, 2008) models, probably through modulating the accumulation of ADO (Fernández et al, 2013) and the expression of profibrotic factors (Fernández et al, 2013)and pro-collagen proteins (Künzli et al, 2008).…”

Section: Adenosine Generation Profibroticmentioning

confidence: 99%

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Targeting Dermal Fibroblast Subtypes in Antifibrotic Therapy: Surface Marker as a Cellular Identity or a Functional Entity?

et al. 2021

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Fibroblasts are the chief effector cells in fibrotic diseases and have been discovered to be highly heterogeneous. Recently, fibroblast heterogeneity in human skin has been studied extensively and several surface markers for dermal fibroblast subtypes have been identified, holding promise for future antifibrotic therapies. However, it has yet to be confirmed whether surface markers should be looked upon as merely lineage landmarks or as functional entities of fibroblast subtypes, which may further complicate the interpretation of cellular function of these fibroblast subtypes. This review aims to provide an update on current evidence on fibroblast surface markers in fibrotic disorders of skin as well as of other organ systems. Specifically, studies where surface markers were treated as lineage markers and manipulated as functional membrane proteins are both evaluated in parallel, hoping to reveal the underlying mechanism behind the pathogenesis of tissue fibrosis contributed by various fibroblast subtypes from multiple angles, shedding lights on future translational researches.

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“…Koo et al demonstrated that a P2X7 receptor antagonist (or P2X7 receptor deficiency in hematopoietic cells) ameliorates murine renal IRI by expansion of regulatory T (Treg) cells. Similarly, apyrase treatment to degrade extracellular ATP protected mice from both acute and chronic renal IRI …”

Section: Targeting Atp In Iri and Graft Preservationmentioning

confidence: 99%

Extracellular nucleotide signaling in solid organ transplantation

Yeudall

Leitinger

Laubach

2020

American Journal of Transplantation

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The role of extracellular purine nucleotides, including adenosine triphosphate (ATP) and adenosine, as modulators of posttransplantation outcome and ischemia‐reperfusion injury is becoming increasingly evident. Upon pathological release of ATP, binding and activation of P2 purinergic surface receptors promote tissue injury and inflammation, while the expression and activation of P1 receptors for adenosine have been shown to attenuate inflammation and limit ischemia‐induced damage, which are central to the viability and long‐term success of allografts. Here we review the current state of the transplant field with respect to the role of extracellular nucleotide signaling, with a focus on the sources and functions of extracellular ATP. The connection between ischemia reperfusion, purinergic signaling, and graft preservation, as well as the role of ATP and adenosine as driving factors in the promotion and suppression of posttransplant inflammation and allograft rejection, are discussed. We also examine novel therapeutic approaches that take advantage of the ischemia‐reperfusion‐responsive and immunomodulatory roles for purinergic signaling with the goal of enhancing graft viability, attenuating posttransplant inflammation, and minimizing complications including rejection, graft failure, and associated comorbidities.

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The Differential Effect of Apyrase Treatment and hCD39 Overexpression on Chronic Renal Fibrosis After Ischemia-Reperfusion Injury

Abstract: A single dose of apyrase administration before IRI protects from both acute and chronic renal injuries and may have clinical application in protection from ischemic-induced renal injury. Furthermore, transgenic expression of hCD39 is associated with increased renal fibrosis after ischemia.

Cited by 16 publications

References 41 publications

TAK1 mediates apoptosis via p38 involve in ischemia-induced renal fibrosis

TAK1 mediates apoptosis via p38 involve in ischemia-induced renal fibrosis

Targeting Dermal Fibroblast Subtypes in Antifibrotic Therapy: Surface Marker as a Cellular Identity or a Functional Entity?

Extracellular nucleotide signaling in solid organ transplantation

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