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| Status |
Public on Dec 07, 2021 |
| Title |
TGF-β-induced miR143/145 influences differentiation, insulin signaling and exercise response in human skeletal muscle [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Physical training improves insulin sensitivity and can prevent type 2 diabetes. However, approximately 20% of individuals lack a beneficial outcome in glycemic control. TGF-β, identified as a possible upstream regulator involved in this low response is also a potent regulator of microRNAs (miRs). Aim of this study was to elucidate the potential impact of TGF-β-driven miRNAs on individual exercise response. Non-targeted long and sncRNA sequencing analyses of TGF-β1-treated human skeletal muscle cells corroborated the effects of TGF-β1 on muscle cell differentiation and the induction of extracellular matrix components, and identified several TGF-β1-regulated miRs. qPCR validated a potent upregulation of miR143/145 and miR181a2 by TGF-β1 in both human myoblasts and differentiating myotubes. Human skeletal muscle biopsy donors participating in a supervised 8-week endurance training intervention (n=40) were categorized as responder based on fold change ISIMats (≥ +1.1) or low responder. In skeletal muscle of low responders, TGF-β signaling and miR143/145 levels were stronger induced by training than in responders. Target-mining revealed HDACs, MYHs and insulin signaling components INSR and IRS1 as potential miR143/145 targets. All these targets were down-regulated in TGF-β1-treated myotubes. Transfection of miR mimics in differentiated myotubes validated MYH1, MYH4, and IRS1 as miR143/145 targets. Elevated TGF-β signaling and miR143/145 induction in skeletal muscle of low responders might obstruct improvements in insulin sensitivity by training in two ways: By negatively impacting cell fusion and myofiber functionality via miR143 suppressing its novel targets MYH1/4; by directly impairing insulin signaling via reduction of INSR by TGF-β and fine-tuned IRS1 suppression by miR143.
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| Overall design |
Human skeletal muscle cells treated with TGF-β1, TGF-β1 + SB431542, or control cells. Data was analysed by RNAseq.
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| Contributor(s) |
Dreher SI, Höckele S, Huypens P, Irmler M, Hoffmann C, Jeske T, Hastreiter M, Moller A, Birkenfeld AL, Häring HU, Peter A, Beckers J, Hrabě de Angelis M, Weigert C |
| Citation(s) |
34943951 |
| |
| Submission date |
Nov 04, 2021 |
| Last update date |
Dec 29, 2021 |
| Contact name |
Johannes Beckers |
| E-mail(s) |
johannes.beckers@helmholtz-munich.de
|
| Organization name |
Helmholtz Zentrum Muenchen
|
| Department |
Institute of Experimental Genetics
|
| Street address |
Ingolstaedter Landstr. 1
|
| City |
Neuherberg |
| ZIP/Postal code |
85764 |
| Country |
Germany |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (15)
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| GSM5673193 |
Human_skeletal_muscle_cells_rep1 [RNA-seq] |
| GSM5673194 |
Human_skeletal_muscle_cells_rep2 [RNA-seq] |
| GSM5673195 |
Human_skeletal_muscle_cells_rep3 [RNA-seq] |
| GSM5673196 |
Human_skeletal_muscle_cells_rep4 [RNA-seq] |
| GSM5673197 |
Human_skeletal_muscle_cells_rep5 [RNA-seq] |
| GSM5673198 |
Human_skeletal_muscle_cells_TGFB1_rep1 [RNA-seq] |
| GSM5673199 |
Human_skeletal_muscle_cells_TGFB1_rep2 [RNA-seq] |
| GSM5673200 |
Human_skeletal_muscle_cells_TGFB1_rep3 [RNA-seq] |
| GSM5673201 |
Human_skeletal_muscle_cells_TGFB1_rep4 [RNA-seq] |
| GSM5673202 |
Human_skeletal_muscle_cells_TGFB1_rep5 [RNA-seq] |
| GSM5673203 |
Human_skeletal_muscle_cells_TGFB1_SB431542_rep1 [RNA-seq] |
| GSM5673204 |
Human_skeletal_muscle_cells_TGFB1_SB431542_rep2 [RNA-seq] |
| GSM5673205 |
Human_skeletal_muscle_cells_TGFB1_SB431542_rep3 [RNA-seq] |
| GSM5673206 |
Human_skeletal_muscle_cells_TGFB1_SB431542_rep4 [RNA-seq] |
| GSM5673207 |
Human_skeletal_muscle_cells_TGFB1_SB431542_rep5 [RNA-seq] |
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| This SubSeries is part of SuperSeries: |
| GSE188236 |
TGF-β Induction of miR-143/145 Is Associated to Exercise Response by Influencing Differentiation and Insulin Signaling Molecules in Human Skeletal Muscle |
|
| Relations |
| BioProject |
PRJNA777956 |
| SRA |
SRP344642 |
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