Biology subjects

Takamori, A.

Publications and source records attributed to Takamori, A..

2 recordsLinked to original sources

bioRxiv2022

Diagnosis of type 2 Diabetes Mellitus (T2DM) using Paired microRNAs

Type 2 Diabetes mellitus (T2DM) is one of the most common diseases in the world and its prevalence ratio is still increasing. Patients with T2DM have diverse pathophysiological changes like as macrovascular, microvascular diseases, cancers as well as abnormal glucose metabolism. Thus, there are urgent needs to develop relevant biomarkers for the broad range of pathophysiology in patients with T2DM. We analyzed the signatures of serum miRNAs with the miRNA array analysis and reverse-transcription based quantitative polymerase chain reaction (RT-qPCR) in 50 patients with type 2 DM (T2DM) and 15 normal subjects. Array analysis showed that 19 miRNAs were up-regulated more than 2-fold and 71 miRNAs were down-regulated less than 0.5 in T2DM in comparison with normal subjects. Top 5 of up-regulated miRNAs were miR-3619-3p, miR-557, miR-6850-5p, miR-3648, miR-4730, and 5 of most down-regulated miRNAs were miR-5100, miR-4454, miR-1260b, miR-7975, miR-6131. We selected 4 miRNAs for validation analysis with RT-qPCR based on the abundance enough for reliable analyses and disease-specificities reported in previous reports. Serum miR-126-3p was down-regulated (3.21-fold, p<0.05) in T2DM, and miR-10a up-regulated (1.94-fold, p<0.05). However, none of single miRNA had significant correlation with clinical data and state. Data of the paired miRNAs: miR-10a and miR-200c, or miR-126 and miR-10a, clearly differentiated T2DM patients from normal subjects (p<0.05). Our study showed the paired-miRNA analyses as the more effective diagnostics for T2DM than the single miRNA analysis.

molecular biology↗

bioRxiv2021

Active Translation Control of CD4 T Cell Activation by Regulatory T Cells

Increased protein synthesis is a hallmark of lymphocyte activation. Regulatory T cells (Tregs) suppress the activation and subsequent effector functions of CD4 effector T cells (Teffs). However, molecular mechanisms that enforce Treg-mediated suppression in CD4 Teff are not fully clear. Control of CD4 Teff activation by Tregs has largely been defined at the transcriptional level, which does not reflect changes in post-transcriptional control. We found that Tregs suppressed activation-induced global protein synthesis in CD4 Teffs prior to cell division. We analyzed genome-wide changes in the transcriptome and translatome of activated CD4 Teffs using two independent approaches. We show that mRNAs encoding for the protein synthesis machinery are regulated at the level of translation in activated Teffs. Strikingly, Tregs suppressed global protein synthesis of CD4 Teffs by specifically inhibiting mRNAs of the translation machinery at the level of mTORC1-mediated translation control. Lastly, we found that the RNA helicase eIF4A inhibitor rocaglamide A (RocA) can suppress CD4 Teff activation in vitro to alleviate inflammatory CD4 Teff activation caused by acute Treg depletion in vivo. These data provide evidence that peripheral tolerance is enforced by Tregs through mRNA translational control in CD4 Teffs. Therefore, therapeutic targeting of the protein synthesis machinery can be expected to mitigate inflammatory responses invoked by Treg loss of function.

immunology↗