Biglycan and decorin gene expression in normal and fibrotic rat liver: Cellular localization and regulatory factors
Biglycan and decorin gene expression in normal and fibrotic rat liver: Cellular localization and regulatory factors
复制标题
正常和纤维化大鼠肝脏中双糖链蛋白聚糖和核心蛋白聚糖基因表达：细胞定位和调控因素
DOI：
10.1002/hep.1840160131
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发表时间：
1992
期刊：
影响因子：
13.5
通讯作者：
A. Gressner
中科院分区：
文献类型：
--
作者：
D. Meyer;N. Krull;K. Dreher;A. Gressner
在正常大鼠的肝脏中以及在由长时间胆管结扎和硫代乙酰胺中毒诱导的纤维化过程中的肝组织中，研究了编码新型小软骨素/硫酸皮肤素蛋白聚糖核心蛋白聚糖和双糖蛋白聚糖的核心蛋白的基因的表达。确定了负责这些转录本表达的细胞类型和一些关键调控因子。在正常肝组织中检测到双糖链蛋白聚糖和核心蛋白聚糖信使RNA。它们的相对丰度在肝纤维化过程中强烈增加，分别在胆总管结扎后8周和口服硫代乙酰胺给药后12周在肝脏组织中达到最高水平。特异性蛋白多糖转录本在正常和再生肝的肝细胞中几乎不存在，在新鲜分离和培养的枯否细胞中仅观察到痕量。储脂细胞清楚地表达双糖链蛋白聚糖和核心蛋白聚糖转录本。在原代培养期间，其信使RNA的稳态水平增加了三倍（双糖链聚糖）和四倍（核心蛋白聚糖）。与原代培养物相比，肌成纤维细胞样细胞（第二次传代后转化的脂肪储存细胞）含有显著降低水平的核心蛋白聚糖信使RNA和更低水平的双糖链蛋白聚糖信使RNA。核心蛋白信使RNA表达的这些变化不能通过35 S标记的培养基蛋白多糖（尤其是培养基硫酸软骨素）的合成速率来反映。来自枯否细胞和肌纤维母细胞样细胞的短暂酸化（但不是天然）条件培养基和转化生长因子-β1使原代培养的脂肪储存细胞中双糖链蛋白聚糖和核心蛋白聚糖信使RNA的相对丰度增加了5倍。肌成纤维细胞样细胞中的双糖蛋白聚糖和核心蛋白聚糖对这些刺激没有反应。相反，转化生长因子-α-条件培养基和天然条件培养基在原代培养中均无效，但在转化的脂肪储存细胞中最有效地提高了这些蛋白聚糖转录物的稳态水平。这些数据为正常和纤维化肝脏中双糖链蛋白聚糖和核心蛋白聚糖的表达提供了证据，这是脂肪储存细胞和肌纤维母细胞样细胞的特性。双糖链蛋白聚糖和核心蛋白聚糖转录水平在贮脂细胞及其转化的对照中受转化生长因子-β1、转化生长因子-α、枯否细胞条件培养基和肌纤维母细胞样细胞条件培养基的差异调节。（肝脏病学1992;16：204-216。）
The expression of genes encoding the core proteins of the novel small chondroitin/dermatan sulfate proteoglycans decorin and biglycan was studied in the livers of normal rats and in liver tissue during fibrogenesis induced by prolonged bile‐duct ligation and thioacetamide poisoning. The cell types responsible for the expression of these transcripts and some key regulatory factors were identified. Both biglycan and decorin messenger RNAs were detected in normal liver tissue. Their relative abundance increased strongly during liver fibrogenesis, reaching highest levels in cirrhotic tissue 8 wk after common bile‐duct ligation and after 12 wk of peroral thioacetamide administration, respectively. Specific proteoglycan transcripts were almost absent in hepatocytes from normal and regenerating liver, and only trace amounts were observed in freshly isolated and cultured Kupffer cells. Fat‐storing cells clearly expressed both biglycan and decorin transcripts. The steady‐state levels of their messenger RNAs increased threefold (biglycan) and fourfold (decorin) during primary culture. Myofibroblastlike cells (transformed fat‐storing cells after the second passage) contained dramatically reduced levels of decorin messenger RNA and also lower levels of biglycan messenger RNA compared with primary cultures. These changes of core protein messenger RNA expression were not reflected by the synthesis rates of medium proteoglycans labeled with35S as Na2SO4, in particular that of medium chondroitin sulfate. Transiently acidified (but not native) conditioned media from Kupffer cells and myofibroblastlike cells and transforming growth factor‐β1 enhanced the relative abundances of biglycan and decorin messenger RNAs up to five times in primary‐cultured fat‐storing cells. Biglycan and decorin in myofibroblastlike cells did not respond to these stimuli. Instead, transforming growth factor‐α‐conditioned and native conditioned media, both inefficient in primary cultures, were most effective in the elevation of the steady‐state levels of these proteoglycan transcripts in transformed fat‐storing cells. The data provide evidence for the expression of both biglycan and decorin in normal and fibrotic liver, which is a property of fat‐storing cells and myofibroblastlike cells. Biglycan and decorin transcript levels are differentially regulated by transforming growth factor‐β1, transforming growth factor‐α, Kupffer cell–conditioned medium and myofibroblastlike cell–conditioned medium in fatstoring cells and their transformed countcrparts. (HEPATOLOGY 1992;16:204–216.)