The protective effects of fibroblast growth factor 10 against hepatic ischemia-reperfusion injury in mice

Li, Santie; Zhu, Zhongxin; Xue, Mei; Pan, Xuebo; Tong, Gaozan; Yi, Xinchu; Fan, Junfu; Li, Yuankuan; Li, Wanqian; Dong, Yetong; Shen, Enzhao; Gong, Wenjie; Wang, Xuejiao; Yu, Ying; Maeng, Yoo Jae; Li, Xiaokun; Lee, Kwang Youl; Jin, Litai; Cong, Weitao

doi:10.1016/j.redox.2021.101859

Cited by 35 publications

(29 citation statements)

References 47 publications

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“…The protective role of PEG35 is also evidenced in the Nrf2-mediated response. The activation of the Nrf2 transcription factor could prevent IR injury, both through the activation of antioxidant and anti-inflammatory pathways [ 38 , 39 , 40 ]. In our study, the preservation of steatotic livers in the IGL-2 solution increased the Nrf2 expression and that of the antioxidant system, HO-1.…”

Section: Discussionmentioning

confidence: 99%

PEG35 and Glutathione Improve Mitochondrial Function and Reduce Oxidative Stress in Cold Fatty Liver Graft Preservation

et al. 2022

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The need to meet the demand for transplants entails the use of steatotic livers, more vulnerable to ischemia-reperfusion (IR) injury. Therefore, finding the optimal composition of static cold storage (SCS) preservation solutions is crucial. Given that ROS regulation is a therapeutic strategy for liver IR injury, we have added increasing concentrations of PEG35 and glutathione (GSH) to the preservation solutions (IGL-1 and IGL-2) and evaluated the possible protection against energy depletion and oxidative stress. Fatty livers from obese Zücker rats were isolated and randomly distributed in the control (Sham) preserved (24 h at 4 °C) in IGL-0 (without PEG35 and 3 mmol/L GSH), IGL-1 (1 g/L PEG35, and 3 mmol/L GSH), and IGL-2 (5 g/L PEG35 and 9 mmol/L GSH). Energy metabolites (ATP and succinate) and the expression of mitochondrial oxidative phosphorylation complexes (OXPHOS) were determined. Mitochondrial carrier uncoupling protein 2 (UCP2), PTEN-induced kinase 1 (PINK1), nuclear factor-erythroid 2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and the inflammasome (NLRP3) expressions were analyzed. As biomarkers of oxidative stress, protein oxidation (AOPP) and carbonylation (DNP derivatives), and lipid peroxidation (malondialdehyde (MDA)–thiobarbituric acid (TBA) adducts) were measured. In addition, the reduced and oxidized glutathione (GSH and GSSG) and enzymatic (Cu–Zn superoxide dismutase (SOD), CAT, GSH S-T, GSH-Px, and GSH-R) antioxidant capacities were determined. Our results showed that the cold preservation of fatty liver graft depleted ATP, accumulated succinate and increased oxidative stress. In contrast, the preservation with IGL-2 solution maintained ATP production, decreased succinate levels and increased OXPHOS complexes I and II, UCP2, and PINK-1 expression, therefore maintaining mitochondrial integrity. IGL-2 also protected against oxidative stress by increasing Nrf2 and HO-1 expression and GSH levels. Therefore, the presence of PEG35 in storage solutions may be a valuable option as an antioxidant agent for organ preservation in clinical transplantation.

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Section: Discussionmentioning

confidence: 99%

PEG35 and Glutathione Improve Mitochondrial Function and Reduce Oxidative Stress in Cold Fatty Liver Graft Preservation

et al. 2022

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“…Adeno‐associated virus (AAV) vectors have been used to express Fgf1 , Fgf2 , Fgf4 , Fgf10 , Fgf16 , Fgf15/19 , Fgf21 , Fgf22 , shFgf22 , Fgfr1 , and shFgfr2 (Frisch et al, 2016; Gadaleta et al, 2020; Haenzi et al, 2016; Jazwa et al, 2010; V. Jimenez, Jambrina, et al, 2018; Li, Wang, Cai, et al, 2018; S. Li, He, et al, 2020; Luo et al, 2018; Madry et al, 2013; Sponton & Kajimura, 2018; Tang et al, 2016; Yu et al, 2016; J. Zhang, Gupte, et al, 2017). AAV‐FGF10 has been shown to protect against hepatic ischemia–reperfusion (IR) injury in mice (S. Li, Zhu, Xue, et al, 2021). Mice injected with AAV‐FGF15/19 (non‐mitogenic variant) showed reduced bile acid synthesis and bile acid pool size and protection from intestinal inflammation (Gadaleta et al, 2020).…”

Section: Tools To Manipulate and Monitor Fgf Signaling In Vitro And I...mentioning

confidence: 99%

“…Zhang, Gupte, et al, 2017). AAV-FGF10 has been shown to protect against hepatic ischemia-reperfusion (IR) injury in mice (S. Li, Zhu, Xue, et al, 2021). Mice injected with AAV-FGF15/19 (non-mitogenic variant) showed reduced bile acid synthesis and bile acid pool size and protection from intestinal inflammation (Gadaleta et al, 2020).…”

Section: Genetic and Viral Vector-mediated Regulation Of Fgf Signalingmentioning

confidence: 99%

New developments in the biology of fibroblast growth factors

Ornitz

Itoh

2022

WIREs Mechanisms of Disease

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The fibroblast growth factor (FGF) family is composed of 18 secreted signaling proteins consisting of canonical FGFs and endocrine FGFs that activate four receptor tyrosine kinases (FGFRs 1-4) and four intracellular proteins (intracellular FGFs or iFGFs) that primarily function to regulate the activity of voltagegated sodium channels and other molecules. The canonical FGFs, endocrine FGFs, and iFGFs have been reviewed extensively by us and others. In this review, we briefly summarize past reviews and then focus on new developments in the FGF field since our last review in 2015. Some of the highlights in the past 6 years include the use of optogenetic tools, viral vectors, and inducible transgenes to experimentally modulate FGF signaling, the clinical use of small molecule FGFR inhibitors, an expanded understanding of endocrine FGF signaling, functions for FGF signaling in stem cell pluripotency and differentiation, roles for FGF signaling in tissue homeostasis and regeneration, a continuing elaboration of mechanisms of FGF signaling in development, and an expanding appreciation of roles for FGF signaling in neuropsychiatric diseases.

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“…This protective role was abolished by NRF2 knockout in mice. Elsewhere, it was found that FGF10 overexpression also increased hepatocyte proliferation in the late phase of IRI [ 44 , 45 ].…”

Section: Hepatic Microenvironmentmentioning

confidence: 99%

Targeting the Hepatic Microenvironment to Improve Ischemia/Reperfusion Injury: New Insights into the Immune and Metabolic Compartments

Gao¹,

Qiu²,

Wang³

et al. 2022

Aging and disease

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Hepatic ischemia/reperfusion injury (IRI) is mainly characterized by high activation of immune inflammatory responses and metabolic responses. Understanding the molecular and metabolic mechanisms underlying development of hepatic IRI is critical for developing effective therapies for hepatic IRI. Recent advances in research have improved our understanding of the pathogenesis of IRI. During IRI, hepatocyte injury and inflammatory responses are mediated by crosstalk between the immune cells and metabolic components. This crosstalk can be targeted to treat or reverse hepatic IRI. Thus, a deep understanding of hepatic microenvironment, especially the immune and metabolic responses, can reveal new therapeutic opportunities for hepatic IRI. In this review, we describe important cells in the liver microenvironment (especially non-parenchymal cells) that regulate immune inflammatory responses. The role of metabolic components in the diagnosis and prevention of hepatic IRI are discussed. Furthermore, recent updated therapeutic strategies based on the hepatic microenvironment, including immune cells and metabolic components, are highlighted.

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The protective effects of fibroblast growth factor 10 against hepatic ischemia-reperfusion injury in mice

Cited by 35 publications

References 47 publications

PEG35 and Glutathione Improve Mitochondrial Function and Reduce Oxidative Stress in Cold Fatty Liver Graft Preservation

PEG35 and Glutathione Improve Mitochondrial Function and Reduce Oxidative Stress in Cold Fatty Liver Graft Preservation

New developments in the biology of fibroblast growth factors

Targeting the Hepatic Microenvironment to Improve Ischemia/Reperfusion Injury: New Insights into the Immune and Metabolic Compartments

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