A regulatory pathway for fibrinogen biosynthesis involving an indirect feedback loop.
A regulatory pathway for fibrinogen biosynthesis involving an indirect feedback loop.
复制标题
纤维蛋白原生物合成的调节途径涉及间接反馈回路。
DOI：
10.1111/j.1749-6632.1982.tb22146.x
复制
发表时间：
1982
影响因子：
5.2
通讯作者：
Ritchie,DG
中科院分区：
文献类型：
--
作者：
Fuller,GM;Ritchie,DG
Fibrinogen is a plasma glycoprotein that is synthesized and secreted by hepatic parenchymal cells. This protein belongs to a group of hepatically derived plasma proteins whose synthesis is markedly increased during an acute inflammatory challenge.'While the precise molecular mechanisms that bring about this dramatic increase in the production of fibrinogen are not known, numerous studies have demonstrated that a variety of hormones may play an important part in the hepatic regulation of fibrinogen synthesis. For example, gl~~ o~ orti~ oids,~*~ certain synthetic steroid hormones,'thyroxin5 and insulin'have all been shown to cause a significant increase in fibrinogen synthesis in hepatocyte monolayer cultures. Furthermore, certain leukocytic products (leukocytic endogenous mediator, LEM; hepatocyte-stimulating factor, HSF) have also been shown to increase fibrinogen production, either when injected into animal^^-^ or when incubated with monolayer cultures of primary hepatocytes.'O~" Of particular interest in this study, however, are the reported observations that certain plasmin-derived fragments of fibrinogen or fibrin, when infused into experimental animals, cause a marked increase in fibrinogen synthesi~.'~~'~ When the two major plasmin-derived fragments of fibrinogen or fibrin (fragments D and E and D'and E', respectively) were isolated and injected into rats only the D fragment was found to be stim~ latory.'~ Additional observations have suggested that only the plasmin-derived fragments of fibrinogen and not fibrin are capable of stimulating synthesis." Finally, it should be pointed out that several investigators have been unable to demonstrate any significant stimulatory response when plasmin-derived fragments were injected into experimental While these studies provide some indirect evidence for the regulation of hepatic fibrinogen synthesis by fibrinogen and/or fibrin degradation products (a possible feedback control loop) more information is required to understand the precise molecular and cellular interactions involved. In an effort to better understand how plasmin-derived fibrinogen and fibrin fragments may control fibrinogen synthesis, we have isolated fragments D and E and tested their effect on fibrinogen synthesis in hepatocyte monolayer cultures. Hepatocytes were unresponsive to the addition of fragments D, E, D', E', as well as fibrinogen itself, indicating that no direct feedback regulatory mechanism exists. However, the production of a monocyte-derived hepatocyte stimulating factor (HSF) was increased in a dose-dependent manner following the addition of these fragments to leukocyte preparations. Since HSF can regulate hepatic
