miRNA effects on gut homeostasis: therapeutic implications for inflammatory bowel disease

Dhuppar, Shivnarayan; Murugaiyan, Gopal

doi:10.1016/j.it.2022.09.003

Cited by 20 publications

(8 citation statements)

References 147 publications

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“…In the context of IBD, dysregulation of miRNA expression has been implicated in the initiation and perpetuation of intestinal inflammation, although little information is available on the role of these molecules in determining resistance or response to medications. MiRNAs orchestrate a complex interplay by targeting the key genes involved in immune modulation, gut microbial homeostasis, epithelial barrier function, and cytokine signaling [ 76 ]. This nuanced regulatory network positions miRNAs as promising candidates not only in understanding the pathogenesis of IBD but also in unraveling their potential role in the development of resistance to therapeutic interventions [ 77 ].…”

Section: Epigenetic Modificationsmentioning

confidence: 99%

Cellular and Molecular Determinants of Biologic Drugs Resistance and Therapeutic Failure in Inflammatory Bowel Disease

Puca,

Capobianco,

Coppola

et al. 2024

IJMS

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The advent of biologic drugs has revolutionized the treatment of Inflammatory Bowel Disease, increasing rates of response and mucosal healing in comparison to conventional therapies by allowing the treatment of corticosteroid-refractory cases and reducing corticosteroid-related side effects. However, biologic therapies (anti-TNFα inhibitors, anti-α4β7 integrin and anti-IL12/23) are still burdened by rates of response that hover around 40% (in biologic-naïve patients) or lower (for biologic-experienced patients). Moreover, knowledge of the mechanisms underlying drug resistance or loss of response is still scarce. Several cellular and molecular determinants are implied in therapeutic failure; genetic predispositions, in the form of single nucleotide polymorphisms in the sequence of cytokines or Human Leukocyte Antigen, or an altered expression of cytokines and other molecules involved in the inflammation cascade, play the most important role. Accessory mechanisms include gut microbiota dysregulation. In this narrative review of the current and most recent literature, we shed light on the mentioned determinants of therapeutic failure in order to pave the way for a more personalized approach that could help avoid unnecessary treatments and toxicities.

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Section: Epigenetic Modificationsmentioning

confidence: 99%

Cellular and Molecular Determinants of Biologic Drugs Resistance and Therapeutic Failure in Inflammatory Bowel Disease

Puca,

Capobianco,

Coppola

et al. 2024

IJMS

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“…Muscle atrophy occurs when the rate of protein degradation exceeds protein synthesis, often induced by factors such as starvation and disease conditions. In many cases, miRNAs have been found to be involved in pathological and physiological stress [ 25 , 26 , 27 , 28 ]. Dysregulated expression of miRNAs in skeletal muscle-related diseases suggests their potential role in protecting or exacerbating skeletal muscle during disease [ 29 , 30 , 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

Transcriptome Analysis of miRNA and mRNA in Porcine Skeletal Muscle following Glaesserella parasuis Challenge

Zhou,

Chen,

Deng

et al. 2024

Genes

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Glaesserella parasuis (G. parasuis) causes systemic infection in pigs, but its effects on skeletal muscle and underlying mechanisms are poorly understood. We investigated G. parasuis infection in colostrum-deprived piglets, observing decreased daily weight gain and upregulation of inflammatory factors in skeletal muscle. Muscle fiber area and diameter were significantly reduced in the treated group (n = 3) compared to the control group (n = 3), accompanied by increased expression of FOXO1, FBXO32, TRIM63, CTSL, and BNIP3. Based on mRNA and microRNA (miRNA) sequencing, we identified 1642 differentially expressed (DE) mRNAs and 19 known DE miRNAs in skeletal muscle tissues between the two groups. We predicted target genes with opposite expression patterns to the 19 miRNAs and found significant enrichment and activation of the FoxO signaling pathway. We found that the upregulated core effectors FOXO1 and FOXO4 were targeted by downregulated ssc-miR-486, ssc-miR-370, ssc-miR-615, and ssc-miR-224. Further investigation showed that their downstream upregulated genes involved in protein degradation were also targeted by the downregulated ssc-miR-370, ssc-miR-615, ssc-miR-194a-5p, and ssc-miR-194b-5p. These findings suggest that G. parasuis infection causes skeletal muscle atrophy in piglets through accelerated protein degradation mediated by the “miRNAs-FOXO1/4” axis, while further research is necessary to validate the regulatory relationships. Our results provide new insights into the understanding of systemic inflammation growth mechanisms caused by G. parasuis and the role of miRNAs in bacterial infection pathogenesis.

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“…Recent evidence indicates that microRNAs (miR) play a crucial role in orchestrating these processes. Mice lacking Dicer 1 (gene encoding microRNA processing enzyme) in intestinal epithelial cells exhibit marked changes in the epithelium with reduced number of goblet cells, increased crypt cell apoptosis and inflammation and impaired barrier ( McKenna et al, 2010 ; Dhuppar and Murugaiyan, 2022 ). No doubt, several microRNAs regulating the expression of key intestinal genes have been reported.…”

mentioning

confidence: 99%

“…No doubt, several microRNAs regulating the expression of key intestinal genes have been reported. For example, miR-181 family works against colonic inflammation and epithelial cell injury ( Jimenez et al, 2022 ), miR-31 is required for epithelial regeneration ( Tian et al, 2017 ), miR-195, miR-802 and miR-429 are essential for goblet and Paneth cell function and several microRNAs are needed for adequate innate immune responses ( Dhuppar and Murugaiyan, 2022 ). Moreover, microRNAs have emerged as key regulators of host and gut microbiota communication that is often disturbed in intestinal diseases ( Dong et al, 2019 ).…”

mentioning

confidence: 99%

“…Since their discovery in 1993 ( Lee et al, 1993 ), microRNAs have been widely explored for their biomarker potential. They are not only expressed in tissues but also exist in biological fluids where their aberrant levels have been correlated with several diseases like gestational diabetes mellitus ( Poirier et al, 2017 ) and colitis ( Tili et al, 2017 ; Dhuppar and Murugaiyan, 2022 ). Fecal microRNAs secreted mainly by the intestinal epithelial cells ( Liu et al, 2016 ) are a recent addition to the microRNA based diagnostic tools ( Ahmed et al, 2009 ; Sarshar et al, 2020 ).…”

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confidence: 99%

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Editorial: The role of MicroRNAs and other non-coding RNAs in gut inflammation and gastrointestinal cancers

Anbazhagan

Rawat

2023

Front. Mol. Biosci.

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miRNA effects on gut homeostasis: therapeutic implications for inflammatory bowel disease

Cited by 20 publications

References 147 publications

Cellular and Molecular Determinants of Biologic Drugs Resistance and Therapeutic Failure in Inflammatory Bowel Disease

Cellular and Molecular Determinants of Biologic Drugs Resistance and Therapeutic Failure in Inflammatory Bowel Disease

Transcriptome Analysis of miRNA and mRNA in Porcine Skeletal Muscle following Glaesserella parasuis Challenge

Editorial: The role of MicroRNAs and other non-coding RNAs in gut inflammation and gastrointestinal cancers

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