Abstract The lipids present in hepatic stellate cells （HSCs） lipid droplets include retinyl ester, triglyceride, cholesteryl ester, cholesterol, phospholipids and free fatty acids. Activation of HSCs is crucial to t...Abstract The lipids present in hepatic stellate cells （HSCs） lipid droplets include retinyl ester, triglyceride, cholesteryl ester, cholesterol, phospholipids and free fatty acids. Activation of HSCs is crucial to the development of fibrosis in liver disease. During activation, HSCs transform into myofibroblasts with concomitant loss of their lipid droplets and production of excessive extracellular matrix. Release of lipid droplets containing retinyl esters and triglyceride is a defining feature of activated HSCs. Accumulating evidence supports the proposal that recovering the accumulation of lipids would inhibit the activation of HSCs. In healthy liver, quiescent HSCs store 80% of total liver retinols and release them depending on the extracellular retinol status. However, in injured liver activated HSCs lose their retinols and produce a considerable amount of extracelhilar matrix, subsequently leading to liver fibrosis. Further findings prove that lipid metabolism of HSCs is closely associated with its activation, yet relationship between activated HSCs and the lipid metabolism has remained mysterious.展开更多
Hepatic stellate cells（HSCs） are a kind of fat-storing cells, the lipid droplets are rich in the Cytoplasm, in which retinyl ester accounts for 42%, triglyceride occupies 28%, cholesterol （total） occupies 13%, pho...Hepatic stellate cells（HSCs） are a kind of fat-storing cells, the lipid droplets are rich in the Cytoplasm, in which retinyl ester accounts for 42%, triglyceride occupies 28%, cholesterol （total） occupies 13%, phospholipids occupies 4% respectively. Studies have continued that thetransforms of HSC phenotype follows the changing of the cell lipid. After the activation of HSC, with HSC phenotype changing from fat-storing cells into myofibroblast, the lipid droplets decreased or disappeared gradually, which means HSCs are under the differentiating process of removing adipose, meawhile triglyceride, and the main content of lipid droplets, also obviously reduced. It was ever declined that during the process of HSC re-fating, the activated HSC would turn into quiescent state. Therefore this shows HSCs fat metabolism is closely related to the biological activity.展开更多
Hepatic stellate cells(HSCs) are a kind of adipocytes. In HSCs lipids mainly exist in the form of lipid droplets. They are abundantly found in the cytoplasm and their main constituents are triglycerides. Lipid metabol...Hepatic stellate cells(HSCs) are a kind of adipocytes. In HSCs lipids mainly exist in the form of lipid droplets. They are abundantly found in the cytoplasm and their main constituents are triglycerides. Lipid metabolism in HSCs is closely related to its biological activity, however the mechanism of lipid droplets disappearance after HSC activation is not clearly established yet. Recent research shows that, cyclooxygenase-2 plays an important regulatory role in the lipid metabolism of HSCs. This paper seeks to review the subject based on studies that have been conducted so far to understand the role of cyclooxygenase-2 in the metabolism of lipids in HSCs.展开更多
Enhanced glycolysis is a distinct feature associated with numerous stem cells and cancer cells.However,little is known about its regulatory roles in gene expression and cell fate determination.Here,we confirm that gly...Enhanced glycolysis is a distinct feature associated with numerous stem cells and cancer cells.However,little is known about its regulatory roles in gene expression and cell fate determination.Here,we confirm that glycolytic metabolism and lactate production decrease during the differentiation of mouse embryonic stem cells(mESCs).Importantly,acidic pH due to lactate accumulation can transiently prevent the silencing of mESC self-renewal in differentiation conditions.Furthermore,acidic pH partially blocks the differentiation of human ESCs(hESCs).Mechanistically,acidic pH downregulates AGO1 protein and de-represses a subset of mRNA targets of miR-290/302 family of microRNAs which facilitate the exit of naive pluripotency state in mESCs.Interestingly,AGO1 protein is also downregulated by acidic pH in cancer cells.Altogether,this study provides insights into the potential function and underlying mechanism of acidic pH in pluripotent stem cells(PSCs).展开更多
基金Partially supported by the National Natural Science Foundation of China(81373465)
文摘Abstract The lipids present in hepatic stellate cells （HSCs） lipid droplets include retinyl ester, triglyceride, cholesteryl ester, cholesterol, phospholipids and free fatty acids. Activation of HSCs is crucial to the development of fibrosis in liver disease. During activation, HSCs transform into myofibroblasts with concomitant loss of their lipid droplets and production of excessive extracellular matrix. Release of lipid droplets containing retinyl esters and triglyceride is a defining feature of activated HSCs. Accumulating evidence supports the proposal that recovering the accumulation of lipids would inhibit the activation of HSCs. In healthy liver, quiescent HSCs store 80% of total liver retinols and release them depending on the extracellular retinol status. However, in injured liver activated HSCs lose their retinols and produce a considerable amount of extracelhilar matrix, subsequently leading to liver fibrosis. Further findings prove that lipid metabolism of HSCs is closely associated with its activation, yet relationship between activated HSCs and the lipid metabolism has remained mysterious.
文摘Hepatic stellate cells（HSCs） are a kind of fat-storing cells, the lipid droplets are rich in the Cytoplasm, in which retinyl ester accounts for 42%, triglyceride occupies 28%, cholesterol （total） occupies 13%, phospholipids occupies 4% respectively. Studies have continued that thetransforms of HSC phenotype follows the changing of the cell lipid. After the activation of HSC, with HSC phenotype changing from fat-storing cells into myofibroblast, the lipid droplets decreased or disappeared gradually, which means HSCs are under the differentiating process of removing adipose, meawhile triglyceride, and the main content of lipid droplets, also obviously reduced. It was ever declined that during the process of HSC re-fating, the activated HSC would turn into quiescent state. Therefore this shows HSCs fat metabolism is closely related to the biological activity.
基金Supported by the National Natural Science Foundation of China(81373465)
文摘Hepatic stellate cells(HSCs) are a kind of adipocytes. In HSCs lipids mainly exist in the form of lipid droplets. They are abundantly found in the cytoplasm and their main constituents are triglycerides. Lipid metabolism in HSCs is closely related to its biological activity, however the mechanism of lipid droplets disappearance after HSC activation is not clearly established yet. Recent research shows that, cyclooxygenase-2 plays an important regulatory role in the lipid metabolism of HSCs. This paper seeks to review the subject based on studies that have been conducted so far to understand the role of cyclooxygenase-2 in the metabolism of lipids in HSCs.
基金This work was supported by the National Key Research and Development Program of China(2016YFA0100701 and 2018YFA0107601)the National Natural Science Foundation of China(91640116,91940302,31622033,and 31821091)the Fundamental Research Funds for the Central Universities(3332018008).
文摘Enhanced glycolysis is a distinct feature associated with numerous stem cells and cancer cells.However,little is known about its regulatory roles in gene expression and cell fate determination.Here,we confirm that glycolytic metabolism and lactate production decrease during the differentiation of mouse embryonic stem cells(mESCs).Importantly,acidic pH due to lactate accumulation can transiently prevent the silencing of mESC self-renewal in differentiation conditions.Furthermore,acidic pH partially blocks the differentiation of human ESCs(hESCs).Mechanistically,acidic pH downregulates AGO1 protein and de-represses a subset of mRNA targets of miR-290/302 family of microRNAs which facilitate the exit of naive pluripotency state in mESCs.Interestingly,AGO1 protein is also downregulated by acidic pH in cancer cells.Altogether,this study provides insights into the potential function and underlying mechanism of acidic pH in pluripotent stem cells(PSCs).
