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Sirt1Regulate The Adipogenesis Of Mesenchymal Stem Cells

Posted on:2015-02-11Degree:MasterType:Thesis
Country:ChinaCandidate:Z J ZhuFull Text:PDF
GTID:2250330428956702Subject:Biochemistry and Molecular Biology
Abstract/Summary:PDF Full Text Request
Mesenchymal stem cell (MSCs) is an important part in stem cells family. As an adult stem cell, MSCs can differentiate to adipocyte, myocyte, bone cells. In recent years, the molecular mechanisms of self-renewal and pluripotency ability in MSCs have been paid a lot of attention. Some genes including Nanong, so×2and oct4, were identified as the core regulator in stem cells to maintain self-renewal and pluripotency ability. In many researches, MSCs prove to be useful in the treatment of many diseases, such as neurodegenerative diseases, lung injury, and spinal cord injury. MSCs also play an important role in the field of regenerative medicine.Sirt1, a member of sirtuin family, is a NAD+-dependent type Ⅲ histone/protein deacetylase and regulates a variety of signal pathway. Sirt1was considered as a positive factor to maintain self-renewal and pluripotency ability in MSCs in some researches. In hematopoietic stem and progenitor cell, sirt1contributes to avoid DNA damage and genomic instability.The role of sirt1in the adipogenesis in MSCs hasn’t received many attentions. In this research, we use ex527, a inhibitor of sirtl which can co-bind with NAD+, and real-time PCR, SA (3-gal staining, oil red O staining to investigate the role of sirt1in adipogenesis in MSCs. The results including:1, the Sirtl inhibitor (ex527) can affect the efficiency of adipogenic differentiation after the start of the MSCs differentiation process; and Sirt1agonists resveratrol does not affect the differentiation efficiency;2, Inhibiting the Nampt activity could significantly inhibit C3H10t adipogenic differentiation efficiency;3, Sirt1inhibitor (NAM) can accelerate aging in the differentiated C3H10t cells4, the Sirtl enzyme inhibitor (ex527) up-regulate the expression of inflammation signaling pathway related genes (IL-6, COX2), down-regulate the expression of autophagy pathway related genes (ATG5, ATG7, Beclinl) and proteasome pathway related genes (FOXO4, PSMD11) in C3H10t cells.
Keywords/Search Tags:SIRT1, MSC, ADIPOGENESIS, AUTOPHAGY, SENESCENCE
PDF Full Text Request
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