ColXV promotes adipocyte differentiation via inhibiting DNA methylation and cAMP/PKA pathway in mice

نویسندگان

  • Guannv Liu
  • Meihang Li
  • Yatao Xu
  • Song Wu
  • Muhammad Saeed
  • Chao Sun
چکیده

Extracellular matrix (ECM), as an essential component of adipose tissue, not only provides mechanical support for adipocyte growth, but also participates in ECM-adipocyte communication via various secreted proteins, including highly enriched collagens. Collagen XV (ColXV) is a secreted non-fibrillar collagen within ECM Basement Membrane (BM) zones and well recognized as a tumor suppressor. However, the role of ColXV in adipose tissue is still unknown. In this study, high fat diet (HFD) fed mice were used as obese model, in which we deeply investigated the interaction between ColXV and adipocyte differentiation or adipose metabolism. We found great elevated ColXV expression and positive effect of ColXV on lipid deposition during adipocyte differentiation or obesity both in vitro and in vivo. cAMP response element binding protein (CREB) is a cellular transcription factor that can inhibit adipogenesis and promote lipolysis. Here we proposed ColXV as a newly discovered downstream gene of CREB. We further proved that CREB can repress adipocyte differentiation and enhance lipolysis by negatively regulating ColXV transcription. Mechanistic studies showed ColXV enhanced adipocyte differentiation and lipid deposition through reducing its DNA methylation and repressing the cAMP/PKA signaling pathway. Collectively, our study identified ColXV as a novel downstream gene for CREB and could promote adipocyte differentiation, inhibit lipolysis through repressing cAMP/PKA signaling pathway and positively regulating adipogenic markers expressions by repressing the activity of maintenance methyltransferase Dnmt1. Our data discovered a novel role of ColXV in adipocyte differentiation and provide insight into obesity and related metabolic diseases.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Study of PKA binding sites in cAMP-signaling pathway using structural protein-protein interaction networks

Backgroud: Protein-protein interaction, plays a key role in signal transduction in signaling pathways. Different approaches are used for prediction of these interactions including experimental and computational approaches. In conventional node-edge protein-protein interaction networks, we can only see which proteins interact but ‘structural networks’ show us how these proteins inter...

متن کامل

Epac, not PKA catalytic subunit, is required for 3T3-L1 preadipocyte differentiation.

Cyclic AMP plays a critical role in adipocyte differentiation and maturation. However, it is not clear which of the two intracellular cAMP receptors, exchange protein directly activated by cAMP/cAMP-regulated guanine nucleotide exchange factor or protein kinase A/cAMP-dependent protein kinase, is essential for cAMP-mediated adipocyte differentiation. In this study, we utilized a well-defined ad...

متن کامل

Activation of Protein Kinase A and Exchange Protein Directly Activated by cAMP Promotes Adipocyte Differentiation of Human Mesenchymal Stem Cells

Human mesenchymal stem cells are primary multipotent cells capable of differentiating into several cell types including adipocytes when cultured under defined in vitro conditions. In the present study we investigated the role of cAMP signaling and its downstream effectors, protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac) in adipocyte conversion of human mesenchymal ...

متن کامل

Cilostazol promotes vascular smooth muscles cell differentiation through the cAMP response element-binding protein-dependent pathway.

OBJECTIVE Cilostazol, a potent type 3 phosphodiesterase inhibitor, has recently been found to reduce neointimal formation by inhibiting vascular smooth muscle cell (VSMC) proliferation. The aim of this study is to investigate whether cilostazol exerts an action on phenotypic modulation of VSMCs, another important process in the pathogenesis of neointimal formation. METHODS AND RESULTS Cilosta...

متن کامل

Evaluation of Changes in Global DNA Methylation during Osteoblastic Differentiation of Mesenchymal Stem Cells: A Laboratory Study

Background and Objectives: Control processes in osteoblastic differentiation of mesenchymal stem cells are not yet fully understood. Epigenetic mechanisms, especially the methylation of CpG Islands in the promoter of genes, are considered as one of the most important control mechanisms in stem cell differentiation. In the process of differentiation, it is debated whether only the methylation of...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 8  شماره 

صفحات  -

تاریخ انتشار 2017