Research for extracellular-matrix remodeling accompanied by liver regeneration

伴随肝再生的细胞外基质重塑研究

基本信息

批准号：
12670486
负责人：
KOIDE Norio
金额：
$ 0.77万
依托单位：
OKAYAMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

Connective tissue growth factor (CTGF) is up-regulated by TGF-β1 during wound healing. Present study was to examine the expression of CTGF during regeneration after 70% partial hepatectomy (PH) or D-galactosamine (GalN) injured liver in rats. CTGF, TGF-β1, and type I collagen mRNAs were semi-quantified by a ribonuclease protection assay. After PH, TGF-β1 and type I collagen were increased at 2-6h and at 12-48h. CTGF increased at 6h, returned to the control level thereafter. Ribonuclease protection assay of cultured hepatic stellate cells (HSC) and in situ hybridization suggest that the cells express CTGF along sinusoid might be HSCs. After GalN-administration, CTGF increased at 2-96h with a shoulder peak at 6-12h followed by a main peak at 24h. TGF-β1 and type I collagen were up-regulated with kinetics similar to those of CTGF. The different kinetics between PH and GalN regenerations indicate that regulation of CTGF in the two processes is different. Higher TGF-β1 expression after infl … More ammatory/necrotic process in the GalN regeneration may caused the prolonged CTGF expression.We examined the expression of CCN (Nov, CYR61 and CTGF) family genes in human hepatocellular carcinomas (HCCs) and studied the correlation of these gene expressions with clinicopathological parameters. Apair of tumor and surrounding non-tumor tissues were obtained from patients with HCC. The presence of mRNA of CCN family genes was analyzed by the reverse-transcription polymerase chain reaction. Nov, CVR61 and CTGF mRNA were identified in 17 (73.9%), 17 (73.9%), six (26.1%) tumors, and in nine (39.1%), 16 (69.6%), one (4.3%) surrounding non-tumor tissues of patients with HCC. No significant difference was found in clinicopathological parameters between cases with HCC negative and positive for these gene expressions. The prevalence of Nov and CTGF expression in HCC is significantly higher than those in surrounding non-tumor. These results suggest that Nov and CTGF is associated with the development of tumors in the liver. Less

结缔组织生长因子 (CTGF) 在伤口愈合过程中被 TGF-β1 上调本研究旨在检测大鼠 70% 部分肝切除 (PH) 或 D-半乳糖胺 (GalN) 损伤肝脏后再生过程中 CTGF 的表达。通过核糖核酸酶保护测定对 CTGF、TGF-β1 和 I 型胶原蛋白 mRNA 进行半定量。PH 后，TGF-β1 和 I 型胶原蛋白在 2-6 小时内增加。 12-48小时，CTGF增加，此后对培养的肝星状细胞(HSC)的核糖核酸酶保护测定和原位杂交表明，在给予GalN后，沿血窦表达CTGF的细胞可能是HSC。 TGF-β1 和 I 型胶原在 2-96 小时增加，并在 6-12 小时出现肩峰，随后在 24 小时出现主峰。上调的动力学与 CTGF 相似。PH 和 GalN 再生之间的不同动力学表明，CTGF 在这两个过程中的调节是不同的。在 GalN 再生过程中，炎症/坏死过程中 TGF-β1 的表达较高。 CTGF 表达延长。我们检测了 CCN（Nov、CYR61 和 CTGF）家族基因在人肝细胞癌 (HCC) 中的表达，并研究了这些基因的相关性通过逆转录聚合酶链反应对 HCC 患者的一对肿瘤和周围非肿瘤组织进行了 CVR61 和 CTGF mRNA 的分析。 (73.9%)、17 例 (73.9%)、6 例 (26.1%) 肿瘤，以及 9 例 (39.1%)、16 例 (69.6%) 1 例(4.3%) HCC患者周围非肿瘤组织中这些基因表达阴性和阳性的HCC病例之间的临床病理参数没有发现显着差异。HCC中Nov和CTGF的表达率显着高于周围组织。这些结果表明 Nov 和 CTGF 与肝脏肿瘤的发展相关。