Yan Wang

Publications (3)5.17 Total impact

• Article: Regulation of Cofilin Activity by CaMKII and Calcineurin.

  Jian-Wu Zhao, Zhong-Li Gao, Qiu-Ye Ji, Hong Wang, Han-Yang Zhang, Yu-Dan Yang, Feng-Juan Xing, Ling-Jie Meng, Yan Wang
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  ABSTRACT: Cofilin promotes actin filament turnover by severing and depolymerizing actin filaments. Cofilin is inactivated by phosphorylation on Ser-3 by LIM-kinase1 (LIMK1) and is activated when protein phosphatase Slingshot-1L (SSH1L) dephosphorylates this residue. The authors have shown that Ca-induced cofilin dephosphorylation is mediated by calcineurin (Cn)-dependent activation of SSH1L. In this study, Ca/calmodulin-dependent protein kinase II (CaMKII) is shown to negatively regulate SSH1L activity and bind to SSH1L in a complex with 14-3-3. Phosphorylation of LIMK1 by CaMKII and its subsequent activation regulates the subcellular localization of SSH1L. Based on these findings, the authors suggest that CaMKII and Cn provide a switch-like mechanism that controls Ca-dependent LIMK1, SSH1L and cofilin activation, and subsequently actin cytoskeletal reorganization.
  The American Journal of the Medical Sciences 01/2012; · 1.39 Impact Factor
• Article: The Role of Slingshot-1L (SSH1L) in the Differentiation of Human Bone Marrow Mesenchymal Stem Cells into Cardiomyocyte-Like Cells.

  Jian-Wu Zhao, Mu-Rui Zhang, Qiu-Ye Ji, Feng-Juan Xing, Ling-Jie Meng, Yan Wang
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  ABSTRACT: Adult cardiomyocytes (CMs) have very limited capacity to regenerate. Therefore, there is a great interest in developing strategies to treat infarcted CMs that are able to regenerate cardiac tissue and promote revascularization of infarcted zones in the heart. Recently, stem cell transplantation has been proposed to replace infarcted CMs and to restore the function of the affected tissue. This area of research has become very active in recent years due to the huge clinical need to improve the efficacy of currently available therapies. Slingshot (SSH) is a family of protein phosphatases, which can specifically dephosphorylate and reactivate cofilin and inhibit the polymerization of actin filaments and actively involved in cytoskeleton rearrangement. In this study, we found that SSH1L promoted morphology changes of microfilaments during differentiation but was inhibited by the inhibitors of actin polymerization such as cytochalasin D. Overexpression of SSH1L could promote cardiac-specific protein and genes expression. 5-Aza can induce the differentiation of hMSCs into cardiomyocyte-like cells in vitro. We also observed that SSH1L efficiently promotes hMSCs differentiation into cardiomyocyte-like cells through regulation and rearrangement of cytoskeleton. Our work provides evidence that supports the positive role of SSH1L in the mechanism of stem cell differentiation into cardiomyocyte-like cells.
  Molecules 01/2012; 17(12):14975-94. · 2.39 Impact Factor
• Article: Differentiation of human mesenchymal stem cells: the potential mechanism for estrogen-induced preferential osteoblast versus adipocyte differentiation.

  Jian-Wu Zhao, Zhong-Li Gao, Hong Mei, Yu-Lin Li, Yan Wang
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  ABSTRACT: Bone marrow-derived mesenchymal stem cells (MSCs) are capable of differentiating into osteoblasts and adipocytes. This critical balance between osteoblast and adipocyte differentiation plays a significant role in maintaining normal bone homeostasis. In osteoporosis, a metabolic bone disease seen mainly in postmenopausal women because of estrogen deficiency, the concomitant occurrence of increased bone marrow adipocyte production with diminished production of osteoblasts, points to the potential role of estrogen in shifting the balance of MSC differentiation. We established an in vitro differentiation model of isolated human MSCs (hMSCs) and examined the role of distinct estrogen signaling pathways in regulating the differentiation of hMSCs. Estrogen promoted the differentiation of hMSCs to osteoblasts in contrast to adipocytes, the former of which was mediated through the PI3K/SSH1L but not the mitogen-activated protein kinase pathway. This study provides a novel mechanistic understanding of estrogen-related osteoporosis and identifies potential targets for antiosteoporosis therapies.
  The American Journal of the Medical Sciences 02/2011; 341(6):460-8. · 1.39 Impact Factor