Wnt信号转导通路与肝纤维化

Wnt信号通路包括经典通路和非经典通路,其参与调控细胞的分化、癌变、凋亡及机体免疫、应激等生理病理过程。最近有研究表明Wnt信号通路与肝星状细胞的活化及肝纤维化的发生相关,深入研究Wnt信号通路在肝纤维化发生中的作用,将有助于进一步揭示肝纤维化的发生机制,为肝纤维化的防治提供新的可能途径及干预靶点。     

长链非编码RNA PVT1通过激活Wnt信号通路对肝癌干细胞自我更新能力的调控

摘 要 目的：探讨长链非编码RNA PVT1通过激活Wnt信号通路对肝癌干细胞自我更新能力的调控作用。 方法: 设HEPG2肝癌干细胞组、LNCRNA PVT1 mimics组、LNCRNA PVT1 inhibitor组,培养结束后,检测各组细胞活力、单克隆形成数目、成球率、凋亡率水平、G1期、PVT1 mRNA、WNT、SWI、SNF蛋白表达水平。 结果: LNCRNA PVT1 mimics组OD值、存活率水平、克隆形成数目、成球率、G1期、PVT1 mRNA、WNT、SWI、SNF蛋白表达水平高于HEPG2肝癌干细胞组（P<0.05）,细胞凋亡率低于HEPG2肝癌干细胞组（P<0.05）;LNCRNA PVT1 inhibitor组OD值、存活率、克隆形成数目、成球率、G1期、PVT1 mRNA、WNT、SWI、SNF蛋白表达水平低于HEPG2肝癌干细胞组、LNCRNA PVT1 mimics 组（P<0.05）,细胞凋亡率高于HEPG2肝癌干细胞组、LNCRNA PVT1 mimics 组(P<0.05)。LNCRNA PVT1 mRNA 与克隆形成数目、成球率、G1期、WNT、SWI、SNF正相关关系明显,与凋亡率负相关关系明显（P<0.05）。 结论: LNCRNA PVT1通过激活SWI/SNF复合物进而激活Wnt信号传导来促进肝癌干细胞的自我更新和肿瘤增殖。     

Osteocytes and mechanical loading: The Wnt connection

Bone adapts to the mechanical forces that it experiences. Orthodontic tooth movement harnesses the cell‐ and tissue‐level properties of mechanotransduction to achieve alignment and reorganization of the dentition. However, the mechanisms of action that permit bone resorption and formation in response to loads placed on the teeth are incompletely elucidated, though several mechanisms have been identified. Wnt/Lrp5 signalling in osteocytes is a key pathway that modulates bone tissue's response to load. Numerous mouse models that harbour knock‐in, knockout and transgenic/overexpression alleles targeting genes related to Wnt signalling point to the necessity of Wnt/Lrp5, and its localization to osteocytes, for proper mechanotransduction in bone. Alveolar bone is rich in osteocytes and is a highly mechanoresponsive tissue in which components of the canonical Wnt signalling cascade have been identified. As Wnt‐based agents become clinically available in the next several years, the major challenge that lies ahead will be to gain a more complete understanding of Wnt biology in alveolar bone so that improved/expedited tooth movement becomes a possibility.     

Wnt/β-catenin信号通路调控Sp5机制的研究进展

摘要：Wnt/β-catenin信号通路是一条广泛存在于生物体内且在进化上具有高度保守特性的通路。该通路在细 胞生长、发育、迁移及凋亡过程中发挥着重要作用。特异性蛋白-5（Sp5）作为Wnt/β-catenin信号通路的下游靶点,在 发育过程中也有着重要的调控作用,包括细胞分化、组织形成及肿瘤的发生等。本文就Wnt/β-catenin信号通路对其 下游分子Sp5的作用进行综述,明确Wnt/β-catenin-Sp5在疾病发展中的作用。     

Current advances of long non-coding RNAs mediated by wnt signaling in glioma

Glioma is the most common and aggressive brain tumor in the central nervous system (CNS), in which Wnt signaling pathway has been verified to play a pivotal role in regulating the initiation and progression. Currently, numerous studies have indicated that long non-coding RNAs (lncRNAs) have critical functions across biological processes including cell proliferation, colony formation, migration, invasion and apoptosis via Wnt signaling pathway in glioma. This review depicts canonical and non-canonical Wnt/β‐catenin signaling pathway properties and relative processing mechanisms in gliomas, and summarizes the function and regulation of lncRNAs mediated by Wnt signaling pathway in the development and progression of glioma. Ultimately, we hope to seek out promising biomarkers and reliable therapeutic targets for glioma.     

Wnt signaling pathway in aging-related tissue fibrosis and therapies

Fibrosis is the final hallmark of pathological remodeling, which is a major contributor to the pathogenesis of various chronic diseases and aging-related organ failure to fully control chronic wound-healing and restoring tissue function. The process of fibrosis is involved in the pathogenesis of the kidney, lung, liver, heart and other tissue disorders. Wnt is a highly conserved signaling in the aberrant wound repair and fibrogenesis, and sustained Wnt activation is correlated with the pathogenesis of fibrosis. In particular, mounting evidence has revealed that Wnt signaling played important roles in cell fate determination, proliferation and cell polarity establishment. The expression and distribution of Wnt signaling in different tissues vary with age, and these changes have key effects on maintaining tissue homeostasis. In this review, we first describe the major constituents of the Wnt signaling and their regulation functions. Subsequently, we summarize the dysregulation of Wnt signaling in aging-related fibrotic tissues such as kidney, liver, lung and cardiac fibrosis, followed by a detailed discussion of its involvement in organ fibrosis. In addition, the crosstalk between Wnt signaling and other pathways has the potential to profoundly add to the complexity of organ fibrosis. Increasing studies have demonstrated that a number of Wnt inhibitors had the potential role against tissue fibrosis, specifically in kidney fibrosis and the implications of Wnt signaling in aging-related diseases. Therefore, targeting Wnt signaling might be a novel and promising therapeutic strategy against aging-related tissue fibrosis.