Research for extracellular-matrix remodeling accompanied by liver regeneration

伴随肝再生的细胞外基质重塑研究

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670486/
• 关键词: extracellular-matrix remodeling; TGF-β; CTGF; liver regeneration; type I collagen; partial hepatectomy; D-galactosamine injured liver; 細胞外マトリックス

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70%肝部分切除（PH）或d -半乳糖胺（GalN）损伤大鼠肝脏再生过程中CTGF的表达。采用核糖核酸酶保护实验对CTGF、TGF-β1和I型胶原mrna进行半定量。PH后，TGF-β1和I型胶原在2-6h和12-48h升高。CTGF在6h时升高，之后恢复到对照水平。体外培养的肝星状细胞（HSC）核糖核酸酶保护实验和原位杂交表明，沿正弦曲线表达CTGF的细胞可能是肝星状细胞。给药后，CTGF在2-96h升高，6-12h出现肩峰，24h出现主峰。TGF-β1和I型胶原蛋白上调，其动力学与CTGF相似。PH和GalN再生的不同动力学表明CTGF在这两个过程中的调控是不同的。灌注后TGF-β1表达升高，GalN再生过程中炎症/坏死增多可能导致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，并研究了这些基因表达与临床病理参数的相关性。从HCC患者的肿瘤和周围非肿瘤组织中获得一对。用逆转录聚合酶链反应分析CCN家族基因mRNA的表达。11、CVR61和CTGF mRNA分别在17例（73.9%）、17例（73.9%）、6例（26.1%）肿瘤组织和9例（39.1%）、16例（69.6%）、1例（4.3%）肝癌周围非肿瘤组织中被检测到。这些基因表达阴性和阳性HCC患者的临床病理参数无显著差异。肝癌组织中Nov和CTGF的表达率明显高于周围非肿瘤组织。这些结果表明，Nov和CTGF与肝脏肿瘤的发展有关。少

项目成果

M. Nakahama et al.: "Expression of perlecan proteoglycan in the infarct zone of mouse myocardial infarction."Journal of Molecular Cell Cardiology.. 32(6). 1087-1100 (2000)

M. Nakahama 等人：“小鼠心肌梗塞梗塞区中基底膜聚糖蛋白多糖的表达。”分子细胞心脏病学杂志.. 32(6)。

山本和秀 他: "肝・胆・膵フロンティア10号"診断と治療社. 6 (2000)

Kazuhide Yamamoto 等：“肝脏/胆道/胰腺前沿第 10 期”诊断和治疗出版 6 (2000)。

M. Nakamura et al.: "Cytoskeletal Inhibitors, Anti-adhesion Molecule Antibodies, and Lectins Inhibit Hepatoyte Spheroid Formation."Acta Medica Okayama. 56(1). 43-50 (2002)

M. Nakamura 等人：“细胞骨架抑制剂、抗粘附分子抗体和凝集素抑制肝细胞球体形成。”冈山医学报。

Kozo Ujike 他: "Kinetics of expression of connective tissue growth factor gene during liver regeneration after partial hepatectomy and D-galactosamine-induced liver injury in rats"Biochemcal and Biophysical Research Communications. 277(2). 448-454 (2000)

Kozo Ujike 等人：“大鼠部分肝切除和 D-半乳糖胺诱导的肝损伤后结缔组织生长因子基因的表达动力学”277(2) 448-454 (2000)。

Shoji Hirasaki 他: "Expression of the human Nov, Cyr61 and CTGF (CCN family) in human hpatocellular carcinoma.."Hepatology Research. 19(掲載予定). (2001)

Shoji Hirasaki 等人：“人肝细胞癌中人 Nov、Cyr61 和 CTGF（CCN 家族）的表达。”Hepatology Research 19（待出版）。