Xinggang Wu - Academia.edu (original) (raw)
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Papers by Xinggang Wu
Blood, Jan 21, 2014
Mutations in HFE are the most common cause of hereditary hemochromatosis (HH). HFE mutations resu... more Mutations in HFE are the most common cause of hereditary hemochromatosis (HH). HFE mutations result in reduced expression of hepcidin, a hepatic hormone, which negatively regulates iron absorption from the duodenum and iron release from macrophages. However, the mechanism by which HFE regulates hepcidin expression in hepatocytes is not well understood. It is known that the bone morphogenetic protein (BMP) pathway plays a central role in controlling hepcidin expression in the liver. Here we show that HFE overexpression increased Smad1/5/8 phosphorylation and hepcidin expression, whereas inhibition of BMP signaling abolished HFE-induced hepcidin expression in Hep3B cells. HFE was found to associate with ALK3, inhibiting ALK3 ubiquitination and proteasomal degradation and increasing ALK3 protein expression and accumulation on the cell surface. The 2 HFE mutants associated with HH, HFE C282Y and HFE H63D, regulated ALK3 protein ubiquitination and trafficking differently, but both failed...
Based on the summary and study of modifications in Barcelona Model,such as the amendments in comp... more Based on the summary and study of modifications in Barcelona Model,such as the amendments in compression line,load-collapse yield surface,suction-increase surface,and different flow rules,the remaining problems in this model were discussed.Results demonstrated that there were many disagreements between them.Apart from the soil properties,different understanding upon its mechanism was the main reason.Regardless of these amendments it was pointed out that some other important effects were not considered in the model,such as how the gradient of critical state line changed with suction,how to consider the coupled effect of load-collapse and suction-increase surface,how to choose suitable stress constants for hydraulic hysteresis study,how to calculate the increase of cohesion due to suction,and how to evaluate the effect of initial structure and depositional history on soil behavior etc.It was extremely difficult and to some extent impractical to modify Barcelona Model to meet all kinds...
Hepcidin is an antimicrobial peptide, which also negatively regulates iron in circulation by cont... more Hepcidin is an antimicrobial peptide, which also negatively regulates iron in circulation by controlling iron absorption from dietary sources and iron release from macrophages. Hepcidin is synthesized mainly in the liver, where hepcidin is regulated by iron loading, inflammation and hypoxia. Recently, we have demonstrated that bone morphogenetic protein (BMP)-hemojuvelin (HJV)-SMAD signaling is central for hepcidin regulation in hepatocytes. Hepcidin is also expressed by macrophages. Studies have shown that hepcidin expression by macrophages increases following bacterial infection, and that hepcidin decreases iron release from macrophages in an autocrine and/or paracrine manner. Although previous studies have shown that lipopolysaccharide (LPS) can induce hepcidin expression in macrophages, whether hepcidin is also regulated by BMPs in macrophages is still unknown. Therefore, we examined the effects of BMP signaling on hepcidin expression in RAW 264.7 and J774 macrophage cell lines,...
Blood, Jan 21, 2014
Mutations in HFE are the most common cause of hereditary hemochromatosis (HH). HFE mutations resu... more Mutations in HFE are the most common cause of hereditary hemochromatosis (HH). HFE mutations result in reduced expression of hepcidin, a hepatic hormone, which negatively regulates iron absorption from the duodenum and iron release from macrophages. However, the mechanism by which HFE regulates hepcidin expression in hepatocytes is not well understood. It is known that the bone morphogenetic protein (BMP) pathway plays a central role in controlling hepcidin expression in the liver. Here we show that HFE overexpression increased Smad1/5/8 phosphorylation and hepcidin expression, whereas inhibition of BMP signaling abolished HFE-induced hepcidin expression in Hep3B cells. HFE was found to associate with ALK3, inhibiting ALK3 ubiquitination and proteasomal degradation and increasing ALK3 protein expression and accumulation on the cell surface. The 2 HFE mutants associated with HH, HFE C282Y and HFE H63D, regulated ALK3 protein ubiquitination and trafficking differently, but both failed...
Based on the summary and study of modifications in Barcelona Model,such as the amendments in comp... more Based on the summary and study of modifications in Barcelona Model,such as the amendments in compression line,load-collapse yield surface,suction-increase surface,and different flow rules,the remaining problems in this model were discussed.Results demonstrated that there were many disagreements between them.Apart from the soil properties,different understanding upon its mechanism was the main reason.Regardless of these amendments it was pointed out that some other important effects were not considered in the model,such as how the gradient of critical state line changed with suction,how to consider the coupled effect of load-collapse and suction-increase surface,how to choose suitable stress constants for hydraulic hysteresis study,how to calculate the increase of cohesion due to suction,and how to evaluate the effect of initial structure and depositional history on soil behavior etc.It was extremely difficult and to some extent impractical to modify Barcelona Model to meet all kinds...
Hepcidin is an antimicrobial peptide, which also negatively regulates iron in circulation by cont... more Hepcidin is an antimicrobial peptide, which also negatively regulates iron in circulation by controlling iron absorption from dietary sources and iron release from macrophages. Hepcidin is synthesized mainly in the liver, where hepcidin is regulated by iron loading, inflammation and hypoxia. Recently, we have demonstrated that bone morphogenetic protein (BMP)-hemojuvelin (HJV)-SMAD signaling is central for hepcidin regulation in hepatocytes. Hepcidin is also expressed by macrophages. Studies have shown that hepcidin expression by macrophages increases following bacterial infection, and that hepcidin decreases iron release from macrophages in an autocrine and/or paracrine manner. Although previous studies have shown that lipopolysaccharide (LPS) can induce hepcidin expression in macrophages, whether hepcidin is also regulated by BMPs in macrophages is still unknown. Therefore, we examined the effects of BMP signaling on hepcidin expression in RAW 264.7 and J774 macrophage cell lines,...