کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10801764 | 1055635 | 2016 | 76 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
miR-29c-3p promotes senescence of human mesenchymal stem cells by targeting CNOT6 through p53-p21 and p16-pRB pathways
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کلمات کلیدی
CCK-8hMSCsSA-β-galImmunofluorescence - ایمونوفلورسانسanalysis of variance - تحلیل واریانسANOVA - تحلیل واریانس Analysis of varianceMesenchymal stem cell - سلول های بنیادی مزانشیمیhuman mesenchymal stem cells - سلول های بنیادی مزانشیمی انسانیcell counting kit-8 - شمارش سلول کیت 8Tissue engineering - مهندسی بافتMicroRNA - میکرو RNA Western blot - وسترن بلاتReplicative senescence - پیری تکراریsenescence-associated-β-galactosidase - پیری زودرس، بتا گالاکتوزیداز
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Mesenchymal stem cells (MSCs) are important seed cells for tissue engineering and are promising targets for cell-based therapies. However, the replicative senescence of MSCs during in vitro culture limits their research and clinical applications. The molecular mechanisms underlying the replicative senescence of MSCs are not fully understood. Evidence suggests that miRNAs play important roles in replicative senescence. A microarray analysis found that the miR-29c-3p level was significantly increased during the MSC senescence process. In our study, we investigated the roles of miR-29c-3p in senescence of MSCs. We cultured MSCs for long periods of time, up and down-regulated the miR-29c-3p expression in MSCs, and examined the senescent phenotype changes. The over-expression of miR-29c-3p led to enhanced senescence-associated-β-galactosidase (SA-β-gal) staining, senescence associated secretory phenotype (SASP), senescence associated heterochromatic foci (SAHF), reduced proliferation ability, retarded osteogenic differentiation and corresponding changes in senescence markers, whereas the miR-29c-3p down-regulation had the opposite results. Dual-luciferase reporter assays demonstrated that CNOT6 is the target gene of miR-29c-3p. Knockdown of CNOT6 confirmed its inhibitory effects on the senescence of MSCs. In addition, Western blot results showed that both the p53-p21 and the p16-pRB pathways were activated during the miR-29c-3p-induced senescence of MSCs. In conclusion, our results demonstrate that miR-29c-3p promotes the senescence of MSCs by targeting CNOT6 through p53-p21 and p16-pRB pathways and highlight the contribution of post-transcriptional regulation to stem cell senescence.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1863, Issue 4, April 2016, Pages 520-532
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1863, Issue 4, April 2016, Pages 520-532
نویسندگان
Jin Shang, Yuan Yao, Xin Fan, Lei Shangguan, Jie Li, Huan Liu, Yue Zhou,