Non-alcoholic fatty liver disease (NAFLD) includes a variety of histological conditions (ranging from liver steatosis and steatohepatitis, to fibrosis and hepatocarcinoma) that are characterized by an increased fat co...Non-alcoholic fatty liver disease (NAFLD) includes a variety of histological conditions (ranging from liver steatosis and steatohepatitis, to fibrosis and hepatocarcinoma) that are characterized by an increased fat content within the liver. The accumulation/deposition of fat within the liver is essential for diagnosis of NAFLD and might be associated with alterations in the hepatic and systemic inflammatory state. Although it is still unclear if each histological entity represents a different disease or rather steps of the same disease, inflammatory processes in NAFLD might influence its pathophysiology and prognosis. In particular, non-alcoholic steatohepatitis (the most inflamed condition in NAFLDs, which more frequently evolves towards chronic and serious liver diseases) is characterized by a marked activation of inflammatory cells and the upregulation of several soluble inflammatory mediators. Among several mediators, cytokines and chemokines might play a pivotal active role in NAFLD and are considered as potential therapeutic targets. In this review, we will update evidence from both basic research and clinical studies on the potential role of cytokines and chemokines in the pathophysiology of NAFLD.展开更多
Serglycin belongs to a family of small proteoglycans with Ser-Gly dipeptide repeats,and it is modified with different types of glycosaminoglycan side chains.Intracellular serglycin affects the retention and secretion ...Serglycin belongs to a family of small proteoglycans with Ser-Gly dipeptide repeats,and it is modified with different types of glycosaminoglycan side chains.Intracellular serglycin affects the retention and secretion of proteases,chemokines,or other cytokines by physically binding to these factors in secretory granules.Extracellular serglycin has been found to be released by several types of human cancer cells,and it is able to promote the metastasis of nasopharyngeal carcinoma cells.Serglycin can bind to CD44,which is another glycoprotein located in cellular membrane.Serglycin's function of promoting cancer cell metastasis depends on glycosylation of its core protein,which can be achieved by autocrine as well as paracrine secretion mechanisms.Further investigations are warranted to elucidate serglycin signaling mechanisms with the goal of targeting them to prevent cancer cell metastasis.展开更多
基金Supported by The Swiss National Science Foundation, No. 32003B-134963/1"Sir Jules Thorn Trust Reg" Foundation+4 种基金Gustave and Simone Prévot Foundation to Montecucco FEU FP7 AtheroRemo, No. 201668Swiss National Science Foundation, No. 310030B-133127Novartis FoundationSwiss Heart Foundation to Mach F
文摘Non-alcoholic fatty liver disease (NAFLD) includes a variety of histological conditions (ranging from liver steatosis and steatohepatitis, to fibrosis and hepatocarcinoma) that are characterized by an increased fat content within the liver. The accumulation/deposition of fat within the liver is essential for diagnosis of NAFLD and might be associated with alterations in the hepatic and systemic inflammatory state. Although it is still unclear if each histological entity represents a different disease or rather steps of the same disease, inflammatory processes in NAFLD might influence its pathophysiology and prognosis. In particular, non-alcoholic steatohepatitis (the most inflamed condition in NAFLDs, which more frequently evolves towards chronic and serious liver diseases) is characterized by a marked activation of inflammatory cells and the upregulation of several soluble inflammatory mediators. Among several mediators, cytokines and chemokines might play a pivotal active role in NAFLD and are considered as potential therapeutic targets. In this review, we will update evidence from both basic research and clinical studies on the potential role of cytokines and chemokines in the pathophysiology of NAFLD.
基金supported by a grant from the State Key Program of National Natural Science Foundation of China (No. 81030043)
文摘Serglycin belongs to a family of small proteoglycans with Ser-Gly dipeptide repeats,and it is modified with different types of glycosaminoglycan side chains.Intracellular serglycin affects the retention and secretion of proteases,chemokines,or other cytokines by physically binding to these factors in secretory granules.Extracellular serglycin has been found to be released by several types of human cancer cells,and it is able to promote the metastasis of nasopharyngeal carcinoma cells.Serglycin can bind to CD44,which is another glycoprotein located in cellular membrane.Serglycin's function of promoting cancer cell metastasis depends on glycosylation of its core protein,which can be achieved by autocrine as well as paracrine secretion mechanisms.Further investigations are warranted to elucidate serglycin signaling mechanisms with the goal of targeting them to prevent cancer cell metastasis.