Tissue regeneration - identification and characterization of new cell surface marker for skin stem cells

组织再生——皮肤干细胞新细胞表面标记物的鉴定和表征

• 批准号: 13470172
• 负责人: YOSHIKAWA Kunihiko
• 金额: $ 9.02万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470172/
• 关键词: Stem cell; STAT3; p130Cas; LIG-1; hair follicle; bulge; Psoriasis; 皮膚; 創傷治癒; Lig-1

Stat3 plays a crucial role in transducing a signal for migration of keratinocyte stem cells. To clarify the role of Stat3 in signaling the migration, we studied the intracellular signaling pathway through an integrin receptor in Stat3-deficient keratinocytes. Stat3-deficient keratinocytes demonstrated increased adhesiveness and fast spreading on a collagen matrix. Stat3-deficient keratinocytes had an increased number of tyrosyl-hyperphosphorylated focal adhesions. Analyses with immunoprecipitation revealed that p130Cas was constitutively hyperphosphorylated on tyrosine residues, while other focal adhesion molecules such as FAK and paxillin were not. These results strongly suggest that Stat3 in keratinocytes plays a critical role in turnover of tyrosine phosphorylation of p130Cas, modulating cell adhesiveness to the substratum leading to growth factor-dependent cell migration.The gene encoding a transmembrane glycoprotein LIG-1, of which extracellular region was organized with the leuci … More ne-rich repeats and immunoglobulin-like domains, was disrupted in mice by gene targeting. LIG-1-deficient mice developed a skin change on the tail and facial area after birth. The affected skin was histologically reminiscent of the epidermis in human common skin disease "psoriasis". The strong expression of LIG-1 mRNA in the bulge area of the hair follicles may suggest the strong expression of LIG-1 in the keratinocyte stem cells. Interestingly, the LIG-1 expression was apparently down-regulated in the psoriatic lesions, suggesting that LIG-1 is involved in the growth regulation of epidermal keratinocytes.Palms and soles differ from other body sites in terms of clinical and histologic appearance, response to mechanical stress, and the distribution of keratin 9. Because keratin 9 is exclusively expressed In the palmoplantar suprabasal keratinocyte layers, it is considered a differentiation marker of palms and soles. We studied palmoplantar mesenchymal influences on keratin 9 induction in nonpalmoplantar epidermis. Although nonpalmoplantar keratinocytes did not express keratin 9 mRNA when cultured with nonpalmoplantar fibroblasts, they did express it in cocultures with palmoplantar fibroblasts derived from papillary dermis. Pure epidermal sheets from nonpalmoplantar skin grafted on the human sole wounds showed transdifferentiation to palmoplantar phenotype and expressed keratin 9. Less

Stat3 在转导角质形成细胞干细胞迁移信号方面发挥着至关重要的作用。为了阐明 Stat3 在信号迁移中的作用，我们研究了 Stat3 缺陷的角质形成细胞中通过整合素受体的细胞内信号传导途径。 Stat3 缺陷的角质形成细胞在胶原蛋白基质上表现出粘附性增强和快速铺展。 Stat3 缺陷的角质形成细胞的酪氨酰过度磷酸化粘着斑数量增加。免疫沉淀分析表明，p130Cas 在酪氨酸残基上发生组成型过度磷酸化，而其他粘着斑分子（例如 FAK 和桩蛋白）则不然。这些结果强烈表明，角质形成细胞中的 Stat3 在 p130Cas 酪氨酸磷酸化的周转中发挥着关键作用，调节细胞对基质的粘附性，导致生长因子依赖性细胞迁移。编码跨膜糖蛋白 LIG-1 的基因，其细胞外区域由亮氨酸组成。更多 ne-rich 重复序列和 免疫球蛋白样结构域在小鼠体内被基因靶向破坏。 LIG-1 缺陷小鼠出生后尾部和面部区域出现皮肤变化。受影响的皮肤在组织学上类似于人类常见皮肤病“牛皮癣”中的表皮。毛囊隆起区LIG-1 mRNA的强表达可能提示角质形成细胞干细胞中LIG-1的强表达。有趣的是，LIG-1的表达在银屑病皮损中明显下调，提示LIG-1参与表皮角质形成细胞的生长调节。手掌和足底在临床和组织学外观、对机械应力的反应以及角蛋白9的分布方面与其他身体部位不同。因为角蛋白9只在掌跖基底上层表达 角质形成细胞层，它被认为是手掌和脚底的分化标志物。我们研究了掌跖间充质对非掌跖表皮角蛋白 9 诱导的影响。虽然非掌跖角化细胞与非掌跖成纤维细胞一起培养时不表达角蛋白 9 mRNA，但它们在与源自乳头状真皮的掌跖成纤维细胞共培养时确实表达角蛋白 9 mRNA。移植在人足底伤口上的非掌跖皮肤的纯表皮片显示出向掌跖表型的转分化并表达角蛋白9。更少

项目成果

Yamaguchi Y, Kubo T, Tarutani M, Sano S, Asada H, Kakibuchi M, Hosokawa K, Itami S, Yoshikawa K.: "Epithelial-mesenchymal interactions in wounds: treatment of palmoplanatar wounds by nonpalmoplantar pure epidermal sheet grafts.."Arch Dermatol. 137(5). 621

Yamaguchi Y、Kubo T、Tarutani M、Sano S、Asada H、Kakibuchi M、Hosokawa K、Itami S、Yoshikawa K.：“伤口中的上皮-间质相互作用：通过非掌跖纯表皮片移植治疗掌跖伤口。”Arch

板見 智: "生涯教育講座:毛包の細胞生物学と疾患"日本皮膚科学会雑誌. 112・3. 225-231 (2002)

伊丹聪：“终身教育课程：细胞生物学和毛囊疾病”日本皮肤病学会杂志112・3（2002）。

Sano S, Takeda 3, Yoshikawa K, Itami S.: "Tissue regeneratian: hair follicle as a model."J Investig Dermatol Symp Proc. 6(1). 43-48 (2001)

Sano S、Takeda 3、Yoshikawa K、Itami S.：“组织再生：毛囊作为模型。”J Investig Dermatol Symp Proc。

Kira M, et al.: "Stat3 deficiency in keratinocytes leads to compromised cell migration through hyperphosphorylation of p130Cas."J Biol Chem.. (in press).

Kira M 等人：“角质形成细胞中的 Stat3 缺陷通过 p130Cas 的过度磷酸化导致细胞迁移受损。”J Biol Chem..（出版中）。

吉良 正浩: "STAT3 deficiency in keratinocytes leads to compromised cell migration through hyperphosphorylation of p130(cas)"J Biol Chem.. 277・15. 12931-12936 (2002)

Masahiro Kira：“角质形成细胞中的 STAT3 缺陷通过 p130(cas) 的过度磷酸化导致细胞迁移受损”J Biol Chem.. 12931-12936 (2002)。