Epigenetic reprogramming of immune cells in injury, repair, and resolution

Placek, Katarzyna; Schultze, Joachim L.; Aschenbrenner, Anna C.

doi:10.1172/jci124619

Cited by 68 publications

(52 citation statements)

References 201 publications

(192 reference statements)

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“…Currently, it is known that epigenetic modifications of liver fibrosis‐related genes in liver fibrosis development . Epigenetic provides to a heritable modulation in gene expression that does not alter the DNA itself . Epigenetic influences generally refer to aberrant DNA methylation and non‐coding RNA (ncRNA) modifications .…”

Section: Introductionmentioning

confidence: 99%

“…[4][5][6] Epigenetic provides to a heritable modulation in gene expression that does not alter the DNA itself. 7,8 Epigenetic influences generally refer to aberrant DNA methylation and non-coding RNA (ncRNA) modifications. 9,10 With regard to the latter, de novo DNA methylation activity catalysed by DNA methyltransferase 3A (DNMT3A) is methylated by addition of transfer methyl groups to the C-5 position in the cytosine ring.…”

Section: Introductionmentioning

confidence: 99%

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Epigenetic silencing of LncRNA ANRIL enhances liver fibrosis and HSC activation through activating AMPK pathway

Yang

Zhang

et al. 2020

J Cellular Molecular Medi

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Long non‐coding RNAs (LncRNAs) and DNA methylation are important epigenetic mark play a key role in liver fibrosis. Currently, how DNA methylation and LncRNAs control the hepatic stellate cell (HSC) activation and fibrosis has not yet been fully characterized. Here, we explored the role of antisense non‐coding RNA in the INK4 locus (ANRIL) and DNA methylation in HSC activation and fibrosis. The expression levels of DNA methyltransferases 3A (DNMT3A), ANRIL, α‐Smooth muscle actin (α‐SMA), Type I collagen (Col1A1), adenosine monophosphate‐activated protein kinase (AMPK) and p‐AMPK in rat and human liver fibrosis were detected by immunohistochemistry, qRT‐PCR and Western blotting. Liver tissue histomorphology was examined by haematoxylin and eosin (H&E), Sirius red and Masson staining. HSC was transfected with DNMT3A‐siRNA, over‐expressing ANRIL and down‐regulating ANRIL. Moreover, cell proliferation ability was examined by CCK‐8, MTT and cell cycle assay. Here, our study demonstrated that ANRIL was significantly decreased in activated HSC and liver fibrosis tissues, while Col1A1, α‐SMA and DNMT3A were significantly increased in activated HSC and liver fibrosis tissues. Further, we found that down‐regulating DNMT3A expression leads to inhibition of HSC activation. Reduction in DNMT3A elevated ANRIL expression in activated HSC. Furthermore, we performed the over expression ANRIL suppresses HSC activation and AMPK signalling pathways. In sum, our study found that epigenetic DNMT3A silencing of ANRIL enhances liver fibrosis and HSC activation through activating AMPK pathway. Targeting epigenetic modulators DNMT3A and ANRIL, and offer a novel approach for liver fibrosis therapy.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Epigenetic silencing of LncRNA ANRIL enhances liver fibrosis and HSC activation through activating AMPK pathway

Yang

Zhang

et al. 2020

J Cellular Molecular Medi

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“…It would be important to mention that complex epigenetic regulation of immune response in stroke is changing from the acute phase (inflammation), over repair phase to establishing homeostasis, or to provoke exaggerated reaction and death [ 76 ]. Contribution to complexity gives spatial distribution of different processes in stroke core, penumbra or unaffected tissues with numerous, overlapping regulatory layers ( Figure 1 ).…”

Section: Epigenetic Regulation Of Immune Response In Strokementioning

confidence: 99%

Genetic Aspects of Inflammation and Immune Response in Stroke

Nikolić

Janković

Petrović³

et al. 2020

IJMS

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Genetic determinants play important role in the complex processes of inflammation and immune response in stroke and could be studied in different ways. Inflammation and immunomodulation are associated with repair processes in ischemic stroke, and together with the concept of preconditioning are promising modes of stroke treatment. One of the important aspects to be considered in the recovery of patients after the stroke is a genetic predisposition, which has been studied extensively. Polymorphisms in a number of candidate genes, such as IL-6, BDNF, COX2, CYPC19, and GPIIIa could be associated with stroke outcome and recovery. Recent GWAS studies pointed to the variant in genesPATJ and LOC as new genetic markers of long term outcome. Epigenetic regulation of immune response in stroke is also important, with mechanisms of histone modifications, DNA methylation, and activity of non-coding RNAs. These complex processes are changing from acute phase over the repair to establishing homeostasis or to provoke exaggerated reaction and death. Pharmacogenetics and pharmacogenomics of stroke cures might also be evaluated in the context of immuno-inflammation and brain plasticity. Potential novel genetic treatment modalities are challenged but still in the early phase of the investigation.

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“…Tissue injuries are followed by an inflammatory reaction, which aims to restore tissue integrity (Placek et al, 2019). This inflammatory process is associated with pathological pain experiences including hypersensitivity to mechanical and heat stimuli known respectively as mechanical allodynia and heat hyperalgesia in human (Berta et al, 2017;Nagy, 2004;Yekkirala et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…The development of hypersensitivities depends on plastic changes, known as sensitisation (a use-dependent increase in the activity and excitability), of neurons involved in nociceptive processing (Woolf & Ma, 2007). Upregulation of TRPV1 expression, TRPV1 translocation from the cytoplasm to the cytoplasmic membrane and post-translational modificationmediated increases in TRPV1 responsiveness and activity significantly contribute to the sensitised state of nociceptive primary sensory neurons and underlay the pivotal role of TRPV1 in the development of hypersensitivities to heat and mechanical stimuli in tissue inflammation (Amadesi et al, 2006;Fukuoka et al, 2002;Ji et al, 2002;Kao et al, 2012;Khan et al, 2008;Moriyama et al, 2005;Premkumar & Ahern, 2000;Rathee et al, 2002;Van Buren et al, 2005;Zhang et al, 2005). Inflammatory mediators including nerve growth factor, bradykinin, prostaglandins (PGs), or ligands of various protease activated receptors (PARs), such as thrombin, mast cell-derived tryptase or kallikrein acting on their cognate receptors on TRPV1-expressing primary sensory neurons, initiate those changes in TRPV1 (Isensee et al, 2014;Ji et al, 2002;Khan et al, 2008;Moriyama et al, 2005;Taiwo et al, 1989;Taiwo & Levine, 1990).…”

Section: Introductionmentioning

confidence: 99%

TRPV1 feed-forward sensitisation depends on COX2 upregulation in primary sensory neurons

Wang

Hui

et al. 2020

Preprint

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Increased activity and excitability (sensitisation) of a series of molecules including the transient receptor potential ion channel, vanilloid subfamily, member 1 (TRPV1) in pain-sensing (nociceptive) primary sensory neurons are pivotal for developing pathological pain experiences in tissue injuries. TRPV1 sensitisation is induced and maintained by two major mechanisms; post-translational and transcriptional changes in TRPV1 induced by inflammatory mediators produced and accumulated in injured tissues, and TRPV1 activation-induced feed-forward signalling. The latter mechanism includes synthesis of TRPV1 agonists within minutes, and upregulation of various receptors functionally linked to TRPV1 within a few hours, in nociceptive primary sensory neurons. Here, we report that a novel mechanism, which contributes to TRPV1 activation-induced TRPV1-sensitisation within ~30 minutes in at least ~30% of TRPV1-expressing cultured murine primary sensory neurons, is mediated through upregulation in cyclooxygenase 2 (COX2) expression and increased synthesis of a series of COX2 products. These findings highlight the importance of feed-forward signalling in sensitisation, and the value of inhibiting COX2 activity to control pain, in nociceptive primary sensory neurons in tissue injuries.

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Epigenetic reprogramming of immune cells in injury, repair, and resolution

Cited by 68 publications

References 201 publications

Epigenetic silencing of LncRNA ANRIL enhances liver fibrosis and HSC activation through activating AMPK pathway

Epigenetic silencing of LncRNA ANRIL enhances liver fibrosis and HSC activation through activating AMPK pathway

Genetic Aspects of Inflammation and Immune Response in Stroke

TRPV1 feed-forward sensitisation depends on COX2 upregulation in primary sensory neurons

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