Adenovirus-mediated hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein suppresses dextran sulfate sodium-induced acute ulcerative colitis in rats

Lv, Yifei; Yang, Xiaofei; Huo, Yujia; Tian, Hong; Li, Shuang; Yin, Yan; Hao, Zhiming

doi:10.1002/ibd.22887

Cited by 15 publications

(19 citation statements)

References 32 publications

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“…Support for this hypothesis comes from our finding that the change in redox status (i.e., the increase in lipid peroxidation) of primary cortical neuronal cultures exposed to NMDA was blocked by the presence of HIP/PAP in the culture medium. This is in keeping with previous findings as to the mode of action of HIP/PAP in vivo in the liver and intestines, where it attenuates free radical damage induced by Fas and dextran sodium sulfate, respectively,39,40 as well as in vitro in primary rat brain neuronal cultures, where it blocks peroxide-induced neurotoxicity 19…”

Section: Discussionsupporting

confidence: 92%

HIP/PAP prevents excitotoxic neuronal death and promotes plasticity

Haldipur

Dupuis

Degos

et al. 2014

Ann Clin Transl Neurol

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ObjectivesExcitotoxicity plays a significant role in the pathogenesis of perinatal brain injuries. Among the consequences of excessive activation of the N-methyl-d-aspartate (NMDA)-type glutamate are oxidative stress caused by free radical release from damaged mitochondria, neuronal death and subsequent loss of connectivity. Drugs that could protect nervous tissue and support regeneration are attractive therapeutic options. The hepatocarcinoma intestine pancreas protein/pancreatitis-associated protein I (HIP/PAP) or Reg3α, which is approved for clinical testing for the protection and regeneration of the liver, is upregulated in the central nervous system following injury or disease. Here, we examined the neuroprotective/neuroregenerative potential of HIP/PAP following excitotoxic brain injury.MethodsWe studied the expression of HIP/PAP and two of its putative effectors, cAMP-regulated phosphoprotein 19 (ARPP19) and growth-associated protein 43 (GAP-43), in the neonatal brain, and the protective/regenerative properties of HIP/PAP in three paradigms of perinatal excitotoxicity: intracerebral injection of the NMDA agonist ibotenate in newborn pups, a pediatric model of traumatic brain injury, and cultured primary cortical neurons.ResultsHIP/PAP, ARPP19, and GAP-43 were expressed in the neonatal mouse brain. HIP/PAP prevented the formation of cortical and white matter lesions and reduced neuronal death and glial activation following excitotoxic insults in vivo. In vitro, HIP/PAP promoted neuronal survival, preserved neurite complexity and fasciculation, and protected cell contents from reactive oxygen species (ROS)-induced damage.InterpretationHIP/PAP has strong neuroprotective/neuroregenerative potential following excitotoxic injury to the developing brain, and could represent an interesting therapeutic strategy in perinatal brain injury.

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Section: Discussionsupporting

confidence: 92%

HIP/PAP prevents excitotoxic neuronal death and promotes plasticity

Haldipur

Dupuis

Degos

et al. 2014

Ann Clin Transl Neurol

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“…Wound healing in diabetic patients is frequently impaired owing to hyper production of pro-inflammatory cytokines, and the antimicrobial protein REG3A has been implicated to regulate uncontrolled inflammatory responses in ulcerative colitis27. We thereby hypothesized that impaired wound healing in diabetes might correlate with an aberrant REG3A expression.…”

Section: Resultsmentioning

confidence: 99%

“…REG3A has been proposed to regulate uncontrolled inflammatory responses in ulcerative colitis27, but was not known to be involved in the regulation of inflammatory responses after skin injury. Here we observed that defective REG3A expression may impair wound healing in diabetes through the exacerbation of TLR3-mediated inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…Besides negative regulators, several antimicrobial peptides or proteins have shown anti-inflammatory effects242526. For instance, the antimicrobial peptide, LL-37, inhibits hyaluronan-activated TLR4/CD44 signalling to decrease the expression of pro-inflammatory cytokines24, and the antimicrobial protein, regenerating islet-derived protein 3A (REG3A), has been implicated to regulate uncontrolled inflammation by reducing pro-inflammatory cytokine production in ulcerative colitis27. However, whether REG3A enables to control TLR-mediated inflammatory responses in diabetic skin wounds remains completely unknown.…”

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confidence: 99%

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Hyperglycaemia inhibits REG3A expression to exacerbate TLR3-mediated skin inflammation in diabetes

Quan

Liu

et al. 2016

Nat Commun

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Dysregulated inflammatory responses are known to impair wound healing in diabetes, but the underlying mechanisms are poorly understood. Here we show that the antimicrobial protein REG3A controls TLR3-mediated inflammation after skin injury. This control is mediated by REG3A-induced SHP-1 protein, and acts selectively on TLR3-activated JNK2. In diabetic mouse skin, hyperglycaemia inhibits the expression of IL-17-induced IL-33 via glucose glycation. The decrease in cutaneous IL-33 reduces REG3A expression in epidermal keratinocytes. The reduction in REG3A is associated with lower levels of SHP-1, which normally inhibits TLR3-induced JNK2 phosphorylation, thereby increasing inflammation in skin wounds. To our knowledge, these findings show for the first time that REG3A can modulate specific cutaneous inflammatory responses and that the decrease in cutaneous REG3A exacerbates inflammation in diabetic skin wounds.

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“…The disease activity index (DAI) was estimated daily (DSS-induced colitis) or weekly (TNBS-induced colitis) in accordance with a well-established scoring system[23]. …”

Section: Methodsmentioning

confidence: 99%

Recombinant adeno-associated virus carrying thymosin β₄suppresses experimental colitis in mice

Zheng¹,

Lv²,

Li³

et al. 2017

WJG

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AIMTo investigate the protective effect of a recombinant adeno-associated virus carrying thymosin β4 (AAV-Tβ4) on murine colitis via intracolonic administration.METHODSAAV-Tβ4 was prepared and intracolonically used to mediate the secretory expression of Tβ4 in mouse colons. Dextran sulfate sodium (DSS) was applied to induce the murine ulcerative colitis, and 2,4,6-trinitrobenzene sulfonic acid (TNBS) was used to establish a mouse colitis model resembling Crohn’s disease. The disease severity and colon injuries were observed and graded to reveal the effects of AAV-Tβ4 on colitis. The activities of myeloperoxidase (MPO) and superoxide dismutase (SOD) and the content of malondialdehyde (MDA) were determined using biochemical assays. Colonic levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-10 were measured using ELISA, and mucosal epithelial cell apoptosis and proliferation were detected by TUNEL assay and immunochemistry, respectively.RESULTSRecombinant AAVs efficiently delivered LacZ and Tβ4 into the colonic tissues of the mice, and AAV-Tβ4 led to a strong expression of Tβ4 in mouse colons. In both the DSS and TNBS colitis models, AAV-Tβ4-treated mice displayed distinctly attenuated colon injuries and reduced apoptosis rate of colonic mucosal epithelia. AAV-Tβ4 significantly reduced inflammatory cell infiltrations and relieved oxidative stress in the inflamed colons of the mice, as evidenced by decreases in MPO activity and MDA content and increases in SOD activity. AAV-Tβ4 also modulated colonic TNF-α, IL-1β and IL-10 levels and suppressed the compensatory proliferation of colonic epithelial cells in DSS- and TNBS-treated mice.CONCLUSIONTβ4 exerts a protective effect on murine colitis, indicating that AAV-Tβ4 could potentially be developed into a promising agent for the therapy of inflammatory bowel diseases.

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Adenovirus-mediated hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein suppresses dextran sulfate sodium-induced acute ulcerative colitis in rats

Abstract: HIP/PAP has a protective effect against DSS-induced colitis in rats via inhibiting inflammation, alleviating oxidative damage, and promoting colonic epithelium regeneration. HIP/PAP might represent a new promising therapeutic strategy in UC.

Cited by 15 publications

References 32 publications

HIP/PAP prevents excitotoxic neuronal death and promotes plasticity

HIP/PAP prevents excitotoxic neuronal death and promotes plasticity

Hyperglycaemia inhibits REG3A expression to exacerbate TLR3-mediated skin inflammation in diabetes

Recombinant adeno-associated virus carrying thymosin β₄suppresses experimental colitis in mice

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Adenovirus-mediated hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein suppresses dextran sulfate sodium-induced acute ulcerative colitis in rats

Abstract: HIP/PAP has a protective effect against DSS-induced colitis in rats via inhibiting inflammation, alleviating oxidative damage, and promoting colonic epithelium regeneration. HIP/PAP might represent a new promising therapeutic strategy in UC.

Cited by 15 publications

References 32 publications

HIP/PAP prevents excitotoxic neuronal death and promotes plasticity

HIP/PAP prevents excitotoxic neuronal death and promotes plasticity

Hyperglycaemia inhibits REG3A expression to exacerbate TLR3-mediated skin inflammation in diabetes

Recombinant adeno-associated virus carrying thymosin β4suppresses experimental colitis in mice

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Resources

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Recombinant adeno-associated virus carrying thymosin β₄suppresses experimental colitis in mice