Histone deacetylase inhibitors improve antisense-mediated exon-skipping efficacy in mdx mice

Bizot, Flavien; Goossens, Remko; Tensorer, Thomas; Дмитриев, С. Н.; Garcı́a, Luis; Aartsma‐Rus, Annemieke; Spitali, Pietro; Goyenvalle, Aurélie

doi:10.1016/j.omtn.2022.11.017

Cited by 5 publications

(1 citation statement)

References 36 publications

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“…These also include histone deacetylases inhibitors, that have been shown to be especially effective at treating inflammation in dystrophic muscle over corticosteroids. In several preclinical studies, small molecule HDAC inhibitors yielded significant functional and morphological benefits to dystrophic muscle, including decreasing the inflammatory infiltrate, and increasing muscle size, quality, and function, as well as improving the therapeutic efficacy of gene therapy approaches ( Consalvi et al, 2011 ; Sincennes et al, 2016 ; Licandro et al, 2021 ; Bizot et al, 2022 ). Importantly, they have also been shown to directly modulate the function of satellite cells.…”

Section: Restoring Satellite Cell Function As a Treatment Strategy Fo...mentioning

confidence: 99%

Satellite cell contribution to disease pathology in Duchenne muscular dystrophy

Kodippili

Rudnicki

2023

Front. Physiol.

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Progressive muscle weakness and degeneration characterize Duchenne muscular dystrophy (DMD), a lethal, x-linked neuromuscular disorder that affects 1 in 5,000 boys. Loss of dystrophin protein leads to recurrent muscle degeneration, progressive fibrosis, chronic inflammation, and dysfunction of skeletal muscle resident stem cells, called satellite cells. Unfortunately, there is currently no cure for DMD. In this mini review, we discuss how satellite cells in dystrophic muscle are functionally impaired, and how this contributes to the DMD pathology, and the tremendous potential of restoring endogenous satellite cell function as a viable treatment strategy to treat this debilitating and fatal disease.

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Section: Restoring Satellite Cell Function As a Treatment Strategy Fo...mentioning

confidence: 99%

Satellite cell contribution to disease pathology in Duchenne muscular dystrophy

Kodippili

Rudnicki

2023

Front. Physiol.

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PTBP3 Mediates IL‐18 Exon Skipping to Promote Immune Escape in Gallbladder Cancer

Zhao,

Zhang

et al. 2024

Advanced Science

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Gallbladder cancer (GBC) is the most common malignant tumor of the biliary system, with poor response to current treatments. Abnormal alternative splicing has been associated with the development of a variety of tumors. Combining the GEO database and GBC mRNA‐seq analysis, it is found high expression of the splicing factor polypyrimidine region‐ binding protein 3 (PTBP3) in GBC. Multi‐omics analysis revealed that PTBP3 promoted exon skipping of interleukin‐18 (IL‐18), resulting in the expression of ΔIL‐18, an isoform specifically expressed in tumors. That ΔIL‐18 promotes GBC immune escape by down‐regulating FBXO38 transcription levels in CD8+T cells to reduce PD‐1 ubiquitin‐mediated degradation is revealed. Using a HuPBMC mouse model, the role of PTBP3 and ΔIL‐18 in promoting GBC growth is confirmed, and showed that an antisense oligonucleotide that blocked ΔIL‐18 production displayed anti‐tumor activity. Furthermore, that the H3K36me3 promotes exon skipping of IL‐18 by recruiting PTBP3 via MRG15 is demonstrated, thereby coupling the processes of IL‐18 transcription and alternative splicing. Interestingly, it is also found that the H3K36 methyltransferase SETD2 binds to hnRNPL, thereby interfering with PTBP3 binding to IL‐18 pre‐mRNA. Overall, this study provides new insights into how aberrant alternative splicing mechanisms affect immune escape, and provides potential new perspectives for improving GBC immunotherapy.

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