Stimulation of interstitial collagenase in co-cultures of rat hepatocytes and sinusoidal cells.
Stimulation of interstitial collagenase in co-cultures of rat hepatocytes and sinusoidal cells.
复制标题
大鼠肝细胞和肝窦细胞共培养物中间质胶原酶的刺激。
DOI：
10.1016/0016-5085(86)90858-9
复制
发表时间：
1986
期刊：
影响因子：
29.4
通讯作者：
Kang,AH
中科院分区：
文献类型：
--
作者：
Kashiwazaki,K;Hibbs,MS;Seyer,JM;Mainardi,CL;Kang,AH
虽然在慢性肝损伤期间观察到的纤维化是一个复杂过程的结果，但终末期肝病中胶原蛋白的显著积累引起了人们对调节患病肝脏中胶原蛋白产生和降解的机制的兴趣。目前的研究已经检查了细胞的相互作用，可能是重要的胶原蛋白降解的调节。虽然在正常肝细胞和肝窦细胞的培养物中观察到最少量的间质胶原酶活性，但在脂多糖存在下这些细胞的共培养物显示胶原酶活性显著增加。当肝细胞从体内用四氯化碳处理的大鼠中获得时，在共培养物中观察到的增强的活性不需要添加脂多糖。这种相互作用的进一步表征表明，胶原溶解活性的增加部分是由于肝细胞对可溶性因子的加工，这刺激了窦状隙细胞群的胶原酶产生。放线菌酮抑制了窦状隙细胞胶原酶活性的增强，表明蛋白质合成是必需的。金属蛋白酶抑制剂可消除蛋白水解活性，但丝氨酸或巯基蛋白酶抑制剂则不然。I型胶原的降解产物是脊椎动物胶原酶所见的典型预期产物。因此，似乎在该共培养系统中检测到的胶原溶解活性增加可归因于窦状隙细胞群产生间质胶原酶。这种细胞-细胞相互作用可能在疾病过程中维持肝脏正常结缔组织结构方面发挥重要作用。
Although the fibrosis observed during chronic liver injury is the result of a complex process, the striking accumulation of collagen in end stage liver disease has provoked interest in the mechanisms that regulate both collagen production and degradation in the diseased liver. The present studies have examined the cell interactions that may be important in the regulation of collagen degradation. Although minimal amounts of interstitial collagenase activity were noted in cultures of normal hepatocytes and sinusoidal cells, the co-cultures of these cells in the presence of lipopolysaccharide showed a substantial increase in collagenase activity. When the hepatocytes were obtained from rats that had been treated with carbon tetrachloride in vivo, the enhanced activity seen in the co-cultures did not require the addition of lipopolysaccharide. Further characterization of this interaction suggested that the increase in collagenolytic activity was partially due to the elaboration of soluble factors by the hepatocyte, which stimulated collagenase production by the sinusoidal cell population. Elaboration of collagenase activity by the sinusoidal cells was inhibited by cycloheximide, suggesting that protein synthesis was required. The proteolytic activity was abrogated by inhibitors of metalloproteinases but not by serine or thiol proteinase inhibitors. The degradation products of type I collagen were typical of the expected products seen with vertebrate collagenases. Thus, it appears that the increased collagenolytic activity detected in this co-culture system is attributable to the production of interstitial collagenase by the sinusoidal cell population. Such cell-cell interactions may play an important role in the maintenance of normal connective tissue structure of the liver during disease processes.