Study for both the establishment of in vivo model system for the development of salivary mucous cyst and its treatment

唾液腺粘液囊肿体内模型系统的建立及其治疗研究

• 批准号: 06557112
• 负责人: AZUMA Masayuki
• 金额: $ 6.53万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06557112/
• 关键词: Human salivary gland duct cells; Cyst; TGF-beta1; MMP-2

We have examined the content of matrix metalloproteinase-2 and -9 (MMP-2, MMP-9) in luminal fluid of extravasation mucoceles. The luminal fluid showed a high level of MMP activity compared with saliva from Wharton's duct. This result suggests that proteolytic enzymes are involved in the pathogenesis of mucoceles. Thus, based on the above observation, we attempted to construct a cyst-like structure in vivo, and analyzed molecular mechanisms in the development of the lesion. When SV40-immortalized normal human salivary gland cells (NS-SV-DC) were treated with TGF-beta1 at the concentration of 1 ng/ml or 5 ng/ml followed by co-inoculation with Matrigel into the backs of nude mice, they formed large cystic structures containing luminal fluid. Analysis of luminal fluids contained in cystic cavity demonstrated a high MMP activity. Northern blot analysis indicated that expression of TGF-beta1 and MMP-2 mRNAs in cells was greatly enhanced by treatment with TGF-beta1. Furthermore, the development of cyst formation was almost completely inhibited by the addition of TIMP-1 into Matrigel. These findings, therefore, suggest that the in vivo cyst formation by TGF-beta1-treated cells is associated with the continuous induction of MMP-2 activity.

我们检测了外渗粘液囊肿管腔液中基质金属蛋白酶-2和-9（MMP-2、MMP-9）的含量。与沃顿管唾液相比，管腔液体显示出高水平的 MMP 活性。该结果表明蛋白水解酶参与粘液囊肿的发病机制。因此，基于上述观察，我们尝试在体内构建囊样结构，并分析病变发展的分子机制。当SV40永生化正常人唾液腺细胞（NS-SV-DC）用浓度为1 ng/ml或5 ng/ml的TGF-β1处理，然后与Matrigel共接种到裸鼠背部时，它们形成含有管腔液体的大囊状结构。对囊腔内液体的分析显示出高 MMP 活性。 Northern印迹分析表明，用TGF-β1处理后，细胞中TGF-β1和MMP-2 mRNA的表达大大增强。此外，在基质胶中添加TIMP-1几乎完全抑制了囊肿形成的发展。因此，这些发现表明，TGF-β1 处理的细胞体内囊肿的形成与 MMP-2 活性的持续诱导有关。

项目成果

東 雅之: "SV40不死化正常ヒト唾液腺細胞における野生型p53の発現" 日本口腔科学会雑誌. 43. 580-585 (1994)

Masayuki Higashi：“野生型 p53 在 SV40 永生化正常人唾液腺细胞中的表达”日本口腔医学会杂志 43. 580-585 (1994)。

Masayuki Azuma: "Lack of expression of transforming growth factor-beta type II receptor associated with malignant progression in human salivary gland cell clones." Int.J.Cancer. (in press).

Masayuki Azuma：“转化生长因子-β II 型受体的表达缺乏与人类唾液腺细胞克隆的恶性进展相关。”

Masayuki Azuma: "Different signal pathways involved in transforming growth factor-β1-induced morphologic change and type IV collagen synthesis in SV40-immortalized normal human salivary gland duct and myoeaithlial cell clone" Arch.Oral Biol.(in press). (1

Masayuki Azuma：“SV40 永生化正常人唾液腺管和肌细胞克隆中转化生长因子-β1 诱导的形态变化和 IV 型胶原蛋白合成中涉及的不同信号通路”Arch.Oral Biol.（出版中）。

Masayuki Azuma: "Expression of wild-type p53 in SV40-immortalized normal human salivary gland cells." J.Jpn.Stomatol.Soc.43. 580-585 (1994)

Masayuki Azuma：“野生型 p53 在 SV40 永生化正常人唾液腺细胞中的表达。”

東 雅之: "SV40不死化正常ヒト唾液腺細胞における野性型p53の発現" 日本口腔科学会雑誌. 43. 580-585 (1994)

Masayuki Higashi：“野生型 p53 在 SV40 永生化正常人唾液腺细胞中的表达”日本口腔医学会杂志 43. 580-585 (1994)。