Wnt信号通路与皮肤创面愈合的关系

创面愈合是由炎性细胞、细胞因子等多种因素共同参与,涉及组织修复、再生、重建的一个复杂有序的病理生理过程。皮肤慢性创面的愈合仍然是临床研究的重点与热点,随着分子生物学的发展,对皮肤创面愈合机制的认识也逐渐深入。Wnt信号通路是一条由Wnt蛋白及其受体、调节蛋白等组成的高度保守的信号通路,参与细胞增殖、凋亡、分化等多种生物学过程。Wnt信号通路作为参与皮肤愈合的信号通路之一,被认为具有调控皮肤及其附属器的发育、诱导皮肤附件的形态发生、调节毛囊的周期生长、促进创面血管新生及上皮重塑等多方面的功能。因此本文试从炎性细胞、成纤维细胞、干细胞、血管新生、表皮新生与毛囊新生等方面对Wnt信号通路与皮肤创面愈合的关系作一综述。     

β—链蛋白在Wnt信号转导途径中的作用

Wnt／β－链蛋白通路参与调控胚胎正常发育和细胞增殖与分化等重要生理过程,正常组织细胞中,该信号通路的上下游调节分子Axin,PAC,GSK3β等通过自稳调节方式,使胞浆内β－链蛋白保持低浓度状态,多种肿瘤细胞有β－链蛋白的异常活化,目前出现了几种针对异常活化的Wnt信号通路的新型抗肿瘤基因治疗措施。     

Wnt信号转导通路与神经发育研究进展

Wnt蛋白是一类分泌型糖蛋白家族,Wnt信号蛋白与细胞表面的多种受体相互作用,参与诸多生命过程。对神经系统发育的研究表明,Wnt信号通路在神经发生,神经祖细胞增值、分化,神经干细胞的自我更新,轴突导向等过程中起重要调控作用。多项研究已经证实,Wnt通路失调与诸多神经系统疾病有密切关系。Wnt信号通路的突变或异常,将会引起神经系统发育缺陷。然而,对Wnt非经典信号通路的研究,尤其是新受体Ryk的调控作用的认识迄今仍不全面。根据国内外相关研究,阐述了经典Wnt信号通路Wnt/β-catenin途径的同时也对Wnt/Ryk非经典信号途径这一研究新领域做了讨论。在非经典信号通路中,Ryk-ICD的剪接对于前体细胞的神经分化起重要作用。本文分析了Wnt/β-catenin和Wnt/Ryk信号通路在神经发育中的作用,有助于深入理解神经发育过程中Wnt信号通路的作用机制。然而,Ryk-ICD引导因子、分子机制等问题仍待进一步研究,而这将有利于理解神经干细胞分化机理。     

非经典Wnt信号通路在心脏发育和干细胞向心肌分化中的作用机制

Wnt信号通路是一种哺乳动物进化保守的信号通路,在心脏发育和干细胞向心肌细胞分化中发挥重要的调控作用。经典Wnt信号通路主要调控早期心肌谱系提交,而非经典Wnt信号通路参与调控后续的心脏发育和分化。本文对非经典Wnt信号通路在心脏发育和干细胞向心肌细胞分化中的作用及其机制作一综述,以期为干细胞移植治疗缺血性心肌病提供参考策略。     

Wnt基因/Wnt信号通路与乳腺癌

Wnt蛋白是一组调控胚胎形成期间细胞间信号传导的高度保守的分泌信号分子.在过去的几年里,由Wnt蛋白触发的不同信号通路已经得到了详尽的研究.Wnt基因与Wnt信号通路组成分子的突变可引起发育缺陷,异常的Wnt信号传导可导致人类疾病包括肿瘤的发生.许多证据都表明,Wnt信号通路的失调与乳腺癌的发生发展密切相关.micro...     

敲减Wingless / Wnt1基因表达对赤拟谷盗发育中的影响

Wnt信号通路是进化中高度保守的一条信号转导途径,在调控动物的胚胎轴向正常发育、胚胎分化、决定细胞极性、维持成体动态平衡等方面发挥重要作用. 该信号通路的异常激活还与肿瘤的发生密切相关. 本实验将体外人工合成的Wingless(Wg)/Wnt1基因dsRNA显微注射入赤拟谷盗晚期幼虫体内,研究Wingless/Wnt1蛋白在赤拟谷盗发育过程中发挥的作用. 实验结果显示,注射 Wingless(wg)/Wnt1基因dsRNA后,赤拟谷盗发育形成的蛹,翅膀宽度减小,翅间距明显增大,且羽化过程也受到严重影响. 此外,qPCR结果表明,赤拟谷盗Wingless(Wg)/Wnt1基因被沉默后,Cadherin-like 和 Smoothened (Smo)基因的表达显著上调,Armadillo-2基因略上调. 这些结果揭示,Wnt-1 信号通路和赤拟谷盗翅膀发育以及成虫羽化过程密切相关. 蛹翅宽减小,翅间距增大,可能是由于调控细胞粘连及细胞形态的Cadherin-like 和Armadillo-2基因的上调所引起.更重要的是,Smo基因的上调,表明了Wnt信号通路和Hedgehog信号通路在赤拟谷盗发育过程中有交互作用.     

Wnt信号通路与高血压疾病的研究进展

Wnt信号分子是一类在无脊椎与脊椎动物的多种组织中广泛表达且进化上高度保守的信号刺激分子,他们在生长、发育、代谢和干细胞调节等多种生物学过程中发挥重要作用。在健康成人的器官中Wnt信号是沉默的,但是在病理情况下Wnt信号激活。近年发现Wnt信号通路在心血管疾病的发生发展过程中扮演重要角色。本文将详细介绍Wnt信号通路,及其与高血压疾病的研究进展,试图将对Wnt信号通路的调控作为治疗高血压疾病的新的方向。     

Wnt信号通路在毛细胞分化和再生过程中的作用

Wnt信号通路在生物发育和维持内环境稳态过程中起着重要作用。Wnt配体通过与Frizzle受体结合参与体轴的形成、细胞分化和细胞命运决定等生命活动。在小鼠内耳发育过程中,Wnt信号通路扮演了重要角色：在内耳发育早期阶段,参与听基板的特化和听泡的形成;在内耳发育后期阶段,调控毛细胞分化及毛细胞纤毛束的定向。本文综述了Wnt信号通路在内耳毛细胞发育分化及再生过程中的研究进展,以期为从事相关领域的科研人员提供参考。     

肾脏发育中信号通路的调控作用

肾脏发育是一个复杂的过程,需要在输尿管芽细胞和基质细胞相互诱导下,引起细胞生长、增殖、分化,从而产生肾单位及各种管状结构,最终发育为成熟的肾脏。在肾脏发育过程中,GDNF/Ret、Wnt、BMP等一系列信号通路参与了发育的调控过程。这些信号通路在肾脏发育的不同阶段或不同位置发挥着重要的调控作用,并且通路之间存在相互的调控,从而形成了一个复杂而精细的调控网络,保证了肾脏的正常发育。文章概括了肾脏发育的过程,总结了肾脏发育过程中相关信号通路对肾脏发育的调控作用以及信号通路之间的相互调控。     

SFRP分子对心脏发育的影响

Wnt信号通路对心脏发育起着重要的作用.分泌型卷曲相关蛋白（SFRP）家族作为调控 Wnt信号的重要分子,对心脏发育和心肌分化的作用也越来越被人们所重视.最近,研究人员们对SFRP家族蛋白有了新的认识,认为它们不仅具有拮抗Wnt的作用,还对Wnt信号的转导有着复杂的调节作用.本文就SFRP分子与Wnt信号转导对心脏发育的影响进行综述.     

Hear the Wnt Ror: how melanoma cells adjust to changes in Wnt

The interplay between canonical and non‐canonical Wnt pathways in development and tumorigenesis is tightly regulated. In this review we will describe the yin and the yang of canonical and non‐canonical Wnt signaling pathways during melanocyte development, and melanoma genesis. Canonical Wnt signaling, represented by Wnts such as Wnt1 and Wnt3A, signals via β‐catenin to promote melanocyte differentiation and tumor development. Non‐canonical Wnt signaling, specifically Wnt5A, regulates canonical pathways, and signals to induce melanoma metastasis. This review will focus on the role of Wnt5A during melanoma progression, and its relationship to canonical Wnt signaling.     

Wg signaling in Drosophila heart development as a pioneering model

The heart is one of the first functional embryonic organs occurring during development. The fundamental developmental processes and genes involved in cardiogenesis are conserved between the invertebrates and vertebrates. In the past fifteen years, one of signaling pathways that has been best characterized in heart development in both invertebrates and vertebrates is the Wg/Wnt signaling pathways. Since our discovery of the Wg signaling required for the early heart development in Drosophila, the past fifteen years have witnessed tremendous progress in the understanding of specific Wnt signaling pathways in vertebrate cardiogenesis. This review will summarize the current state of knowledge of Wg signaling transduction in Drosophila heart development, which will benefit our understanding of vertebrate cardiogenesis and human congenital malformations.     

Wnt与MAPK信号通路在肿瘤发生中的串话

Wnt和MAPK信号通路在生物进化过程中高度保守,参与调控胚胎发育和细胞增殖、分化及凋亡等。Wnt和MAPK信号通路调控失常可导致胚胎发育异常和肿瘤形成。近年来发现这两条信号通路在肿瘤发生发展中存在着大量串话（crosstalk）,彼此之间相互调节,共同发挥促癌或抑癌作用,因此,更好地了解两条通路是如何在肿瘤形成中发生交叉对话对于将来肿瘤治疗非常有价值。     

Regulation of hematopoiesis and the hematopoietic stem cell niche by Wnt signaling pathways

Hematopoietic stem cells （HSCs） are a rare population of cells that are responsible for life-long generation of blood cells of all lineages. In order to maintain their numbers, HSCs must establish a balance between the opposing cell fates of self-renewal （in which the ability to function as HSCs is retained） and initiation of hematopoietic differentiation. Multiple signaling pathways have been implicated in the regulation of HSC cell fate. One such set of pathways are those activated by the Wnt family of ligands. Wnt signaling pathways play a crucial role during embryogenesis and deregulation of these pathways has been implicated in the formation of solid tumors. Wnt signaling also plays a role in the regulation of stem cells from multiple tissues, such as embryonic, epidermal, and intestinal stem cells. However, the function of Wnt signaling in HSC biology is still controversial. In this review, we will discuss the basic characteristics of the adult HSC and its regulatory microenvironment, the ＂niche＂, focusing on the regulation of the HSC and its niche by the Wnt signaling pathways.     

Neural crest cells development and neuroblastoma progression: Role of Wnt signaling

Neuroblastoma (NB) is one of the most common heterogeneous extracranial cancers in infancy that arises from neural crest (NC) cells of the sympathetic nervous system. The Wnt signaling pathway, both canonical and noncanonical pathway, is a highly conserved signaling pathway that regulates the development and differentiation of the NC cells during embryogenesis. Reports suggest that aberrant activation of Wnt ligands/receptors in Wnt signaling pathways promote progression and relapse of NB. Wnt signaling pathways regulate NC induction and migration in a similar manner; it regulates proliferation and metastasis of NB. Inhibiting the Wnt signaling pathway or its ligands/receptors induces apoptosis and abrogates proliferation and tumorigenicity in all major types of NB cells. Here, we comprehensively discuss the Wnt signaling pathway and its mechanisms in regulating the development of NC and NB pathogenesis. This review highlights the implications of aberrant Wnt signaling in the context of etiology, progression, and relapse of NB. We have also described emerging strategies for Wnt-based therapies against the progression of NB that will provide new insights into the development of Wnt-based therapeutic strategies for NB.     

Dishevelled activates Ca2+ flux,PKC, and CamKII in vertebrate embryos

Wnt ligands and Frizzled (Fz) receptors have been shown to activate multiple intracellular signaling pathways. Activation of the Wnt-beta-catenin pathway has been described in greatest detail, but it has been reported that Wnts and Fzs also activate vertebrate planar cell polarity (PCP) and Wnt-Ca2+ pathways. Although the intracellular protein Dishevelled (Dsh) plays a dual role in both the Wnt-beta-catenin and the PCP pathways, its potential involvement in the Wnt-Ca2+ pathway has not been investigated. Here we show that a Dsh deletion construct, XDshDeltaDIX, which is sufficient for activation of the PCP pathway, is also sufficient for activation of three effectors of the Wnt-Ca2+ pathway: Ca2+ flux, PKC, and calcium/calmodulin-dependent protein kinase II (CamKII). Furthermore, we find that interfering with endogenous Dsh function reduces the activation of PKC by Xfz7 and interferes with normal heart development. These data suggest that the Wnt-Ca2+ pathway utilizes Dsh, thereby implicating Dsh as a component of all reported Fz signaling pathways.     

A spoonful of sugar makes the melanoma go: the role of heparan sulfate proteoglycans in melanoma metastasis

Heparan sulfate proteoglycans (HSPGs) have been shown to regulate signaling in many systems and are of increasing interest in cancer. While these are not the only sugars to drive melanoma metastasis, HSPGs play important roles in driving metastatic signaling cascades in melanoma. The ability of these proteins to modulate ligand-receptor interactions in melanoma has been quite understudied. Recent data from several groups indicate the importance of these ligands in modulating key signaling pathways including Wnt and fibroblast growth factor (FGF) signaling. In this review, we summarize the current knowledge regarding the structure and function of these proteoglycans and their role in melanoma. Understanding how HSPGs modulate signaling in melanoma could lead to new therapeutic approaches via the dampening or heightening of key signaling pathways.