br Conclusions A simplified schematic
Conclusions A simplified schematic model is proposed (see Fig. 7) illustrating how Lox and Twist are involved in the BMP4-induced EMT-like response and adipocyte lineage commitment. In brief, BMP4 results in increased expression of Lox (Huang et al., 2009) and Twist thus promotes the EMT-like response and adipocyte lineage commitment. Twist could be involved in Lox-dependent effects on the EMT-like response during adipocyte lineage commitment. This study presents molecular insights into cell fate decisions in the adipocyte lineage.
Acknowledgments This research is partially supported by the National Key Basic Research Project Grant 2011CB910201 and 2011CBA01103, the State Key Program of National Natural Science Foundation31030048C120114, Shanghai Key Science and Technology Research Project10JC1401000 (for Q.Q.T.), and National Natural Science Foundation Grant 30700403 and 81170781 (to H.H.). The Department of Biological Chemistry is supported by Shanghai Leading Academic Discipline Project, Project Number: B110. We thank Ya-Lin Huang (Institute of Stem Cell and Regenerative Medicine, Fudan University) for her technical support in confocal microscopy. We also want to thank Dr. Duanqing Pei for providing us with pMX-E-cadherin plasmids.
Introduction Scleroderma (systemic sclerosis, SSc) is a connective tissue disease characterized by vascular injury, the excessive accumulation of extracellular matrix (ECM) proteins in the skin and various internal organs, and immunological abnormalities (Yamamoto, 2009). SSc is resistant to all types of treatments (Yamamoto, 2009). Endothelial buy Radicicol (ECs) are affected in the early stages of SSc (Gabrielli et al., 2009; Kahaleh, 2008). In early lesions there are changes of the endothelial phenotype or EC apoptosis in the absence of EC proliferation or precursor differentiation (Gabrielli et al., 2009; Kahaleh, 2008). It has been reported that mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) from SSc patients show abnormalities in differentiation to ECs (Cipriani et al., 2007; Trojanowska, 2010). Recently, clinical improvement in patients with SSc has been demonstrated following administration of high dose immunosuppressive therapy and autologous hematopoietic cell transplantation (Fleming et al., 2008). Additionally, it has been demonstrated that isolated EPCs from normal peripheral blood participate and increase the formation of new blood vessels (Asahara et al., 1999; Isner et al., 2001). However, isolation of EPCs from adults has limited replicative capacity. In elderly patients with cardiovascular risk factors, EPCs are few in number and dysfunctional (Heeschen et al., 2004; Hill et al., 2003; Vasa et al., 2001). The discovery of human embryonic stem (hESCs) (Thomson et al., 1998) and human-induced pluripotent stem cells (hiPSCs) (Takahashi et al., 2007; Yu et al., 2007), due to their capacities for self-renewal and pluripotency, have provided fascinating possibilities and hopes for curing diseases that have poor prognoses. Until now, several reports have described the differentiation and functionality of ECs derived from murine (Kim and von Recum, 2009; Li et al., 2007; Sone et al., 2003; Yamashita et al., 2000), primate (Kaufman et al., 2004; Sone et al., 2003), and human (Levenberg et al., 2002; Li et al., 2011) ESCs or iPSCs (Li et al., 2011; Rufaihah et al., 2011). The beneficial influences of hESC-derived ECs (hESC-ECs) in the setting of myocardial or limb ischemia has been reported (James et al., 2010; Kane et al., 2010; Levenberg et al., 2002, 2010; Li et al., 2009; Nourse et al., 2010; Rufaihah et al., 2010; Sone et al., 2007). Transplantation of hiPSC-ECs also enhanced capillary density and improved reperfusion in a limb ischemia mouse model (Rufaihah et al., 2011). However, no study has yet reported the therapeutic potential of hESC-ECs or hiPSC-ECs in the treatment of damaged vessels that result from SSc.
Materials and methods