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UHRF1 通过抑制过氧化物酶体增殖物激活受体促进人脂肪干细胞的增殖并抑制脂肪生成。

UHRF1 Promotes Proliferation of Human Adipose-Derived Stem Cells and Suppresses Adipogenesis via Inhibiting Peroxisome Proliferator-Activated Receptor .

机构信息

Department of Endocrinology, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, China.

出版信息

Biomed Res Int. 2019 Jul 22;2019:9456847. doi: 10.1155/2019/9456847. eCollection 2019.

Abstract

Once the adipose tissue is enlarged for the purpose of saving excess energy intake, obesity may be observed. Ubiquitin-like with PHD and RING Finger domains 1 (UHRF1) is helpful in repairing damaged DNA as it increases the resistance of cancer cells against cytocidal drugs. Peroxisome proliferator-activated receptor (PPAR), an important nucleus transcription factor participating in adipogenesis, has been extensively reported. To date, no study has indicated whether UHRF1 can regulate proliferation and differentiation of human adipose-derived stem cells (hADSCs). Hence, this study aimed to utilize overexpression or downregulation of UHRF1 to explore the possible mechanism of proliferation and differentiation of hADSCs. We here used lentivirus, containing UHRF1 (LV-UHRF1) and siRNA-UHRF1 to transfect hADSCs, on which Cell Counting Kit-8 (CCK-8), cell growth curve, colony formation assay, and EdU proliferation assay were applied to evaluate proliferation of hADSCs, cells cycle was investigated by flow cytometry, and adipogenesis was detected by Oil Red O staining and Western blotting. Our results showed that UHRF1 can promote proliferation of hADSCs after overexpression of UHRF1, while proliferation of hADSCs was reduced through downregulation of UHRF1, and UHRF1 can control proliferation of hADSCs through transition from G1-phase to S-phase; besides, we found that UHRF1 negatively regulates adipogenesis of hADSCs via PPAR . In summary, the results may provide a new insight regarding the role of UHRF1 on regulating proliferation and differentiation of hADSCs.

摘要

一旦脂肪组织为了储存多余的能量摄入而增大,就可能会出现肥胖。泛素样含 PH 结构域和环指结构域蛋白 1(UHRF1)有助于修复受损的 DNA,因为它提高了癌细胞对细胞毒性药物的抵抗力。过氧化物酶体增殖物激活受体(PPAR)是参与脂肪生成的重要核转录因子,已经得到了广泛的报道。迄今为止,尚无研究表明 UHRF1 是否可以调节人脂肪来源干细胞(hADSCs)的增殖和分化。因此,本研究旨在利用 UHRF1 的过表达或下调来探讨 hADSCs 增殖和分化的可能机制。我们使用了含有 UHRF1 的慢病毒(LV-UHRF1)和 siRNA-UHRF1 转染 hADSCs,通过细胞计数试剂盒-8(CCK-8)、细胞生长曲线、集落形成实验和 EdU 增殖实验来评估 hADSCs 的增殖,通过流式细胞术研究细胞周期,通过油红 O 染色和 Western blot 检测脂肪生成。我们的结果表明,UHRF1 过表达后可以促进 hADSCs 的增殖,而 UHRF1 下调则降低了 hADSCs 的增殖,UHRF1 可以通过从 G1 期到 S 期的转变来控制 hADSCs 的增殖;此外,我们发现 UHRF1 通过 PPAR 负调控 hADSCs 的脂肪生成。综上所述,这些结果可能为 UHRF1 调节 hADSCs 增殖和分化的作用提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8461/6681597/0c7173dce535/BMRI2019-9456847.001.jpg

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