CAJ | 학술논문

肝星状细胞(hepatic stellate cells,HSCs)在肝脏纤维化发生过程中起着关键作用.当正常肝脏受到损伤时,HSCs由静息状态转分化为类肌成纤维细胞,并保持这种处于激活状态的表型,它们接收到的凋亡和存活的生物信号将决定激活态HSCs的最终细胞寿命.HSCs凋亡的发生与一系列复杂而又相互关联的生物信号传导和调控有关,HSCs凋亡信号来自于细胞膜受体,如死亡受体、神经生长因子受体和外周型苯甲二氮卓受体(peripheral-type benzodiazepine receptor);以及胞浆蛋白,如Bcl-2家族蛋白和细胞周期蛋白等.HSCs存活信号受到多种激酶和细胞因子的诱导,如金属蛋白酶组织抑制剂-1(tissue jnhibitors of metalloproteinase-1)、Rho/Rho激酶、血小板源生长因子(platelet-derived growth factor)、转化生长因子-β1(transforming growth factor-β1)和胰岛素样生长因子(insulin-like growth factor-1)等.特异性地诱导HSCs发生凋亡是治疗肝脏纤维化的直接和有效手段,虽然目前对HSCs由激活态到静息状态的转归尚需进一步研究,但诱导HSCs凋亡将是治疗肝脏纤维化和肝硬化的研究热点和主要发展方向.
간성상세포(hepatic stellate cells,HSCs)재간장섬유화발생과정중기착관건작용.당정상간장수도손상시,HSCs유정식상태전분화위류기성섬유세포,병보지저충처우격활상태적표형,타문접수도적조망화존활적생물신호장결정격활태HSCs적최종세포수명.HSCs조망적발생여일계렬복잡이우상호관련적생물신호전도화조공유관,HSCs조망신호래자우세포막수체,여사망수체、신경생장인자수체화외주형분갑이담탁수체(peripheral-type benzodiazepine receptor);이급포장단백,여Bcl-2가족단백화세포주기단백등.HSCs존활신호수도다충격매화세포인자적유도,여금속단백매조직억제제-1(tissue jnhibitors of metalloproteinase-1)、Rho/Rho격매、혈소판원생장인자(platelet-derived growth factor)、전화생장인자-β1(transforming growth factor-β1)화이도소양생장인자(insulin-like growth factor-1)등.특이성지유도HSCs발생조망시치료간장섬유화적직접화유효수단,수연목전대HSCs유격활태도정식상태적전귀상수진일보연구,단유도HSCs조망장시치료간장섬유화화간경화적연구열점화주요발전방향.
Hepatic stellate cells (HSCs) play an important role in hepatic fibrogenesis.In response to liver injury, HSCs undergo a process called activation, which involves 2 stepsinitiation from quiescent phenotype to myofibroblast-like phenotype, and perpetuation that maintains the activated phenotype of HSCs. The fate of the activated HSCs depends on the apoptotic and survival signals that they receive. The apoptosis of HSCs results from a series of complex and interrelated signaling events. Apoptotic signals for the activated HSCs include proteins from membrane receptors, such as death receptors, nerve growth factor receptor and peripheral-type benzodiazepine receptor, as well as proteins from cytoplasm such as Bcl-2 family members. The survival signals for the activated HSCs are induced by some kinases and cytokines including tissue inhibitors of metalloproteinase-1, Rho/Rho kinase, platelet-derived growth factor, transforming growth factor beta-l, and insulin-like growth factor-1. Approaches that specifically initiate HSC apoptosis are promising to be direct and effective strategies to treat liver fibrosis. Although it remains unclear whether the activated HSCs could be reversed back to the quiescent phenotype,the different expression and sensitivity of pro-apoptotic and survival molecules between quiescent and activated HSCs provide a prospect to develop therapeutic approaches that specifically targets apoptosis of the activated HSCs. These therapeutic strategies to induce HSC apoptosis are current research hotspot and the future for the patients with liver fibrosis and cirrhosis.