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17β-Estradiol (E2) is an important regulator of energy homeostasis and glucose metabolism, thus making it a potential target for preventing or treating metabolic disorders. However, the exact mechanism by which E2 affects high glucose-induced oxidative stress remains unclear. Therefore, the present study investigated the role of E2 in high glucose-induced mitochondrial reactive oxygen species (mtROS) production through estrogen receptor (ER)-mediated signaling in human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) in vitro. In addition, the effect of hUCB-MSC transplantation on mouse skin wound healing induced by E2 in ovariectomized (OVX) diabetic mice in vivo was also studied. High glucose (D-glucose, 25mM) increased mtROS production, resulting in increase of Beclin1 expression and the LC3-II/LC3-I ratio, leading to decreased cell viability. Conversely, E2 (10nM) treatment significantly decreased high glucose-induced mtROS levels and subsequently restored cell viability, suggesting that E2 serves as a strong antioxidant. High glucose downregulated Nrf2 levels in nucleus, subsequently culminating in Sirt3 downregulation and manganese superoxide dismutase (MnSOD) acetylation. However, we found that E2 induces nuclear Nrf2 expression via interaction with ERα. The increased nuclear translocation of Nrf2 triggered Sirt3 upregulation and MnSOD activation, both of which play important roles in decreasing mtROS levels. Thus, the therapeutic effect of hUCB-MSC transplantation on skin wound healing in OVX diabetic mice was enhanced by E2 treatment compared with the findings in OVX diabetic mice treated only with hUCB-MSCs. In addition, blood vessels with well-developed branches were observed in OVX diabetic mice that underwent hUCB-MSC transplantation and E2 treatment compared with the effects of ERα siRNA-transfected hUCB-MSC transplantation alone. In conclusion, our results imply that E2 protects cells against high glucose-induced mtROS production and autophagic cell death through increasing nuclear translocation of Nrf2, which was followed by Sirt3 upregulation and MnSOD activation in hUCB-MSCs.
This article was published in the following journal.
Name: Free radical biology & medicine
Calcium Supplementation Enhanced Adipogenesis and Improved Glucose Homeostasis Through Activation of Camkii and PI3K/Akt Signaling Pathway in Porcine Bone Marrow Mesenchymal Stem Cells (pBMSCs) and Mice Fed High Fat Diet (HFD).
It has been implicated that calcium supplementation is involved in reducing body weight/fat and improving glucose homeostasis. However, the underlying mechanisms are still not fully understood. Here, ...
Mesenchymal stem cells (MSCs) are multipotent cells that can be widely used in stem cell therapy. However, few studies have revealed the potential mechanisms of the changes in aging MSC.
Stem cells are undifferentiated cells located in different parts of the body. The major role of stem cells is to restore of injured tissues. Since the discover of stem cells, they gained a big attenti...
Perinatal tissues possess numerous types of stem (stromal) cells, which are considered effective candidates for cell therapy. These tissues possess common characteristics of both embryonic and adult s...
Mesenchymal stem cells (MSCs) can be considered as an effective tool for bone regeneration. It is variable to find new agents with low cytotoxicity and high efficiency for induction of MSCs into osteo...
The purpose of this study is to determine the safety and efficacy of intrathecal treatment delivered to the cerebrospinal fluid (CSF) of mesenchymal stem cells in ALS patients every 3 mont...
The purpose of this study is verify the efficacy and safety of Human Umbilical Cord Mesenchymal Stem Cells (UC-MSC) therapy for patients with Osteoarthritis, and in addition, provide basis...
To assess the safety of a single dose of IV infusion of bone-marrow derived autologous Mesenchymal Stem Cells (MSCs) in Multiple Sclerosis (MS) with progressive disease status.
This study will evaluate the safety and efficacy of mesenchymal stem cells in patients with cirrhosis of liver. Stem cells will be injected into the hepatic artery. Improvement in various ...
The main hypothesis of the investigators study is that the development of autoimmune diabetes may be halted att diagnosis by the immune modulatory properties of mesenchymal stem cells.
Bone-marrow-derived, non-hematopoietic cells that support HEMATOPOETIC STEM CELLS. They have also been isolated from other organs and tissues such as UMBILICAL CORD BLOOD, umbilical vein subendothelium, and WHARTON JELLY. These cells are considered to be a source of multipotent stem cells because they include subpopulations of mesenchymal stem cells.
Transfer of MESENCHYMAL STEM CELLS between individuals within the same species (TRANSPLANTATION, HOMOLOGOUS) or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS).
Cells that can develop into distinct mesenchymal tissue such as BONE; TENDONS; MUSCLES; ADIPOSE TISSUE; CARTILAGE; NERVE TISSUE; and BLOOD and BLOOD VESSELS.
Colony-forming cells which give rise to NEOPLASMS. They have properties similar to normal stem cells, i.e., high proliferative and self-renewal capacities.
Specialized stem cells that are committed to give rise to cells that have a particular function; examples are MYOBLASTS; MYELOID PROGENITOR CELLS; and skin stem cells. (Stem Cells: A Primer [Internet]. Bethesda (MD): National Institutes of Health (US); 2000 May [cited 2002 Apr 5]. Available from: http://www.nih.gov/news/stemcell/primer.htm)
Track and monitor developments in stem cell research and commercial development. Follow the tabs above to read the latest global news, research, clinical trials on stem cells and follow companies active in the stem cell industry. BioPort...
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Organ transplantation is the moving of an organ from one body to another or from a donor site to another location on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative ...