Identification and characterization of Wnt signaling pathway in keloid pathogenesis.
Identification and characterization of Wnt signaling pathway in keloid pathogenesis.
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DOI：
10.7150/ijms.5349
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发表时间：
2013
影响因子：
3.6
通讯作者：
Ghazizadeh M
中科院分区：
文献类型：
--
作者：
Igota S;Tosa M;Murakami M;Egawa S;Shimizu H;Hyakusoku H;Ghazizadeh M
瘢痕疙瘩的特征是成纤维细胞增殖和大量胶原合成。大量研究表明，无翅型（Wnt）信号通路在细胞增殖、分化、存活、凋亡和迁移等多种功能中发挥着重要作用。本研究的目的是阐明Wnt信号通路在瘢痕疙瘩发病机制中的作用。使用原代成纤维细胞培养物和来自瘢痕疙瘩和正常外观真皮的组织样品。采用半定量RT-PCR、Western blot或免疫组织化学方法评估Wnt家族成员卷曲蛋白（FZD）4受体、受体酪氨酸激酶样孤儿受体（ROR）2和Wnt信号下游靶点糖原合成酶激酶（GSK）3-β和β-连环蛋白的表达。在Wnt家族成员中，与正常成纤维细胞（NF）相比，瘢痕疙瘩成纤维细胞（KF）中Wnt 5a mRNA和蛋白水平升高。KF中β-catenin蛋白的表达也较高。在NF和KF中均未观察到可检测水平的FZD 4受体和ROR 2蛋白。功能分析表明，重组Wnt 5a肽处理NF和KF后，总β-catenin和Ser 33/37/Thr 41磷酸化β-catenin蛋白水平增加，但Ser 45/Thr 41磷酸化β-catenin蛋白水平无明显变化。此外，总GSK 3-β蛋白的表达不受影响，但其磷酸化/失活形式在NF和KF中增加。我们的研究结果强调了Wnt/β-catenin经典信号通路在瘢痕疙瘩发病机制中的潜在作用，从而为治疗调节提供了新的分子靶点。
Keloid is characterized by fibroblastic cell proliferation and abundant collagen synthesis. Numerous studies have shown that the Wingless type (Wnt) signaling pathways play key roles in various cellular functions including proliferation, differentiation, survival, apoptosis and migration. The aim of this study was to clarify the role of Wnt signaling pathway in keloid pathogenesis. Primary fibroblast cultures and tissue samples from keloid and normal appearing dermis were used. The expression of Wnt family members, frizzled (FZD)4 receptor, receptor tyrosine kinase-like orphan receptor (ROR)2 and the Wnt signaling downstream targets, glycogen synthase kinase (GSK)3-β and β-catenin were assessed using semi-quantitative RT-PCR, Western blot, or immunohistochemical methods. Of the Wnt family members, Wnt5a mRNA and protein levels were elevated in keloid fibroblasts (KF) as compared to normal fibroblasts (NF). A higher expression of β-catenin protein was also found in KF. No detectable levels of FZD4 receptor and ROR2 proteins were observed in both NF and KF. Functional analysis showed that treatment of NF and KF with recombinant Wnt5a peptide resulted in an increase in protein levels of total β-catenin and phosphorylated β-catenin at Ser33/37/Thr 41 but no significant change in phosphorylated β-catenin at Ser45/Thr 41 positions. In addition, the expression of total GSK3-β protein was not affected but its phosphorylated/inactivated form was increased in NF and KF. Our findings highlight a potential role for a Wnt/β-catenin canonical signaling pathway triggered by Wnt5a in keloid pathogenesis thereby providing a new molecular target for therapeutic modulations.
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影响因子：
64.5
作者：
Chan, SK;Struhl, G
通讯作者：
Struhl, G
DOI：
10.1073/pnas.102657399
发表时间：
2002-05-14
影响因子：
11.1
作者：
Cheon, SS;Cheah, AYL;Alman, BA
通讯作者：
Alman, BA
影响因子：
3.3
作者：
Ghazizadeh, M;Ogawa, H;Aihara, K
通讯作者：
Aihara, K
影响因子：
19
作者：
Green JL;Kuntz SG;Sternberg PW
通讯作者：
Sternberg PW
DOI：
10.1073/pnas.0712148105
发表时间：
2008-02-26
影响因子：
11.1
作者：
Fukuda, Tetsuya;Chen, Liguang;Kipps, Thomas J.
通讯作者：
Kipps, Thomas J.