Association analysis of RAC1 single nucleotide polymorphisms with ulcerative colitis

Taher, Mohammad; Daryani, Nasser Ebrahimi; Hedayat, Mona; Eslamian, Mohammad; Farhadi, Elham; Mahmoudi, Mahdi; Shirzad, Samira; Taromlou, Mohammd Kazem Nouri; Chaharmahali, Meghedi; Nicknam, Mohammad Hossein; Bashashati, Mohammad; Rezaei, Nima

doi:10.1016/j.clinre.2017.03.002

Cited by 2 publications

(2 citation statements)

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“…S7A). Among them, RAC1 was found to be involved in autoimmune diseases by regulating ERK1/2 signaling [ 23 , 34 ]. Thus, we hypothesized that T lymphocyte-derived sEV miR-142-3p may also affect thyrocyte cell function by targeting RAC1 to inhibit the ERK1/2 signaling pathway.…”

Section: Resultsmentioning

confidence: 99%

miR-142-3p encapsulated in T lymphocyte-derived tissue small extracellular vesicles induces Treg function defect and thyrocyte destruction in Hashimoto’s thyroiditis

Huang

et al. 2023

BMC Med

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Background Hashimoto’s thyroiditis (HT) is an organ-specific autoimmune disease characterized by lymphocyte infiltration that destroys thyrocyte cells. The aim of the present study was to elucidate the role and mechanisms of tissue small extracellular vesicle (sEV) microRNAs (miRNAs) in the pathogenesis of HT. Methods Differentially expressed tissue sEV miRNAs were identified between HT tissue and normal tissue by RNA sequencing in the testing set (n = 20). Subsequently, using quantitative real-time polymerase chain reaction (qRT‒PCR) assays and logistic regression analysis in the validation set (n = 60), the most relevant tissue sEV miRNAs to HT were verified. The parental and recipient cells of that tissue sEV miRNA were then explored. In vitro and in vivo experiments were further performed to elucidate the function and potential mechanisms of sEV miRNAs that contribute to the development of HT. Results We identified that miR-142-3p encapsulated in T lymphocyte-derived tissue sEVs can induce Treg function defect and thyrocyte destruction through an intact response loop. Inactivation of miR-142-3p can effectively protect non-obese diabetic (NOD).H-2h4 mice from HT development display reduced lymphocyte infiltration, lower antibody titers, and higher Treg cells. Looking at the mechanisms underlying sEV action on thyrocyte destruction, we found that the strong deleterious effect mediated by tissue sEV miR-142-3p is due to its ability to block the activation of the ERK1/2 signaling pathway by downregulating RAC1. Conclusions Our findings highlight the fact that tissue sEV-mediated miR-142-3p transfer can serve as a communication mode between T lymphocytes and thyrocyte cells in HT, favoring the progression of HT.

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Section: Resultsmentioning

confidence: 99%

miR-142-3p encapsulated in T lymphocyte-derived tissue small extracellular vesicles induces Treg function defect and thyrocyte destruction in Hashimoto’s thyroiditis

Huang

et al. 2023

BMC Med

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“…Interestingly, whether the association between Rac2 and IBD is based on the function of Rac2 in the NADPH complex is controversial [ 7 , 8 ]. The Rac1 SNPs rs10951982 and rs4720672 are associated with UC [ 10 ], and another Rac1 SNP, rs34932801, was found to lead to poorer thiopurine treatment effect in adult CD patients [ 11 ]; however, the association between Rac1 SNPs and UC was not observed in another study [ 12 ]. In addition, mice with a genetic deletion of RhoA in intestinal epithelial cells (IECs) exhibited spontaneous chronic intestinal inflammation, and RhoA signaling was found to be downregulated in CD patients [ 13 ].…”

Section: Geneticsmentioning

confidence: 99%

Role of Rho GTPases in inflammatory bowel disease

Zhang

Zhou

et al. 2023

Cell Death Discov.

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Rat sarcoma virus homolog (Rho) guanosine triphosphatases (GTPases) function as “molecular switch” in cellular signaling regulation processes and are associated with the pathogenesis of inflammatory bowel disease (IBD). This chronic intestinal tract inflammation primarily encompasses two diseases: Crohn’s disease and ulcerative colitis. The pathogenesis of IBD is complex and considered to include four main factors and their interactions: genetics, intestinal microbiota, immune system, and environment. Recently, several novel pathogenic components have been identified. In addition, potential therapies for IBD targeting Rho GTPases have emerged and proven to be clinically effective. This review mainly focuses on Rho GTPases and their possible mechanisms in IBD pathogenesis. The therapeutic possibility of Rho GTPases is also discussed.

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Association analysis of RAC1 single nucleotide polymorphisms with ulcerative colitis

Cited by 2 publications

References 12 publications

miR-142-3p encapsulated in T lymphocyte-derived tissue small extracellular vesicles induces Treg function defect and thyrocyte destruction in Hashimoto’s thyroiditis

miR-142-3p encapsulated in T lymphocyte-derived tissue small extracellular vesicles induces Treg function defect and thyrocyte destruction in Hashimoto’s thyroiditis

Role of Rho GTPases in inflammatory bowel disease

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