Role of connective tissue growth factor (CTGF) in association with systemic sclerosis

结缔组织生长因子（CTGF）与系统性硬化症相关的作用

• 批准号: 10670785
• 负责人: TAKEHARA Kazuhiko
• 金额: $ 2.05万
• 依托单位: KANAZAWA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670785/
• 关键词: TGF-β; CTGF; systemic sclerosis; fibrosis; CTGE; 繊維化

In these studies, we investigated the role of CTGF, namely inter action with TGF-β in TGF-β induced skin fibrosis model of newborn mice.TGF-β solely induced fibrosis disappears with 3 day peak, although when CTGF was injected simultaneously or consecutively, combination of TGF-β and CTGF induces irreversible fibrosis.Above observations strongly support our hypothesis that TGF-β induces skin fibrosis and CTGF acts to maintain this fibrosis. In addition, we tried to block this fibrosis using anti- CTGF neutralizing antibody, we conformed partial suppression. We are going to screen more potent neutralizing antibody and antisense of DNA.We measured serum CTGF levels of systemic sclerosis using increased cases, we found elevated levels of CTGF the patients and the levels of CTGF was statistically correlated with severity of skin sclerosis and pulmonary fibrosis. Thus, we found strong correlation between CTGF and systemic sclerosis, which is a representative fibrotic disorder.In the future, we use our skin sclerosis mice model by TGF-β and CTGF to screen anti-scleroderma drugs.

本研究探讨了CTGF在TGF-β诱导的新生小鼠皮肤纤维化模型中的作用，即与TGF-β的相互作用，TGF-β单独诱导的纤维化在3天后达到高峰，但当同时或连续注射CTGF时，TGF-β和CTGF联合诱导的纤维化不可逆，上述观察结果有力地支持了我们的假设，即TGF-β诱导皮肤纤维化，CTGF起维持这种纤维化的作用。另外，我们尝试用抗CTGF中和抗体阻断这种纤维化，证实了部分抑制.本研究采用递增法检测了系统性硬化症患者血清CTGF水平，发现患者血清CTGF水平升高，且CTGF水平与皮肤硬化和肺纤维化的严重程度有统计学相关性。因此，我们发现CTGF与代表性纤维化疾病系统性硬化症之间存在很强的相关性，未来我们将利用我们的TGF-β和CTGF皮肤硬化小鼠模型来筛选抗硬皮病药物。

项目成果

Sato S, Nagaoka T, Hasegawa M, et al: "Serum levels of CTGF are elevated in patients with systemic sclerosis : Association with the extent of skin sclerosis and the severity of pulmonary fibrosis"J Rheumatol. 27. 149-154 (2000)

Sato S、Nagaoka T、Hasekawa M 等人：“系统性硬化症患者的血清 CTGF 水平升高：与皮肤硬化程度和肺纤维化严重程度相关”J Rheumatol。

Shinozaki M, Kawara S, Hayashi N, Kakinuma T, Igarashi A, Takehara K: "Induction of subcutaneous fibrosis in newborn mice by transforming growth Factor β-simultaneous application with basic fibroblast growth factor causes persistent fibrosis"Biochem Bioph

Shinozaki M、Kawara S、Hayashi N、Kakinuma T、Igarashi A、Takehara K：“通过转化生长因子 β 诱导新生小鼠皮下纤维化 - 同时应用碱性成纤维细胞生长因子会导致持续性纤维化”Biochem Bioph

M.Hasegawa, S.Sato, K.Kikuchi, K.Takehara: "Antigen specificity of antihistone antibodies in systemic scierosis" Annals of the Rheumatic Diseases. 57(8). 470-475 (1998)

M.Hasekawa、S.Sato、K.Kikuchi、K.Takehara：“系统性硬化症中抗组蛋白抗体的抗原特异性”风湿病年鉴。

Mori T, Kawara S, Shinozaki M, Hayashi N, Kakinuma T, Igarashi A, Takigawa M, Nakanishi T, Takehara K: "Role and interaction of connective tissue growth factor with transforming growth factor-β in persistent fibrosis : A mouse fibrosis model"J Cell Physio

Mori T、Kawara S、Shinozaki M、Hayashi N、Kakinuma T、Igarashi A、Takikawa M、Nakanishi T、Takehara K：“结缔组织生长因子与转化生长因子-β 在持续性纤维化中的作用和相互作用：小鼠纤维化模型《细胞生理学杂志》

Shinozaki M, Kawara S, Hayashi N, Kakinuma T, Igarashi A, Takehara K: "Induction of subcutaneous tissue fibrosis in newborn mice by transforming growth Factor β-simultaneous application with basic fibroblast growth factor causes persistent fibrosis"Bioche

Shinozaki M、Kawara S、Hayashi N、Kakinuma T、Igarashi A、Takehara K：“通过转化生长因子 β 诱导新生小鼠皮下组织纤维化 - 同时应用碱性成纤维细胞生长因子会导致持续性纤维化”Bioche