更新于：2024-09-19

WNT9B

更新于：2024-09-19

基本信息

别名

Protein Wnt-14b、Protein Wnt-15、Protein Wnt-9b

+ [4]

简介

Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Functions in the canonical Wnt/beta-catenin signaling pathway. Required for normal embryonic kidney development, and for normal development of the urogenital tract, including uterus and part of the oviduct and the upper vagina in females, and epididymis and vas deferens in males. Activates a signaling cascade in the metanephric mesenchyme that induces tubulogenesis. Acts upstream of WNT4 in the signaling pathways that mediate development of kidney tubules and the Muellerian ducts. Plays a role in cranofacial development and is required for normal fusion of the palate during embryonic development (By similarity).

关联

100 项与 WNT9B 相关的临床结果

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100 项与 WNT9B 相关的转化医学

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0 项与 WNT9B 相关的专利（医药）

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205

项与 WNT9B 相关的文献（医药）

2024-11-01·Journal of Environmental Sciences

Prenatal prednisone exposure disturbs fetal kidney development and its characteristics

Article

作者: Wang, Wen ; Liu, Yutang ; Yang, Tianshu ; Xia, Zhiping ; Wang, Songdi ; Ao, Ying ; Wang, Hui

Prednisone is a synthetic glucocorticoid that is commonly used in both human and veterinary medication. Now, it is also recognized as an emerging environmental contaminant. Pregnant women may be exposed to prednisone actively or passively through multiple pathways and cause developmental toxicity to the fetus. However, the impact of prenatal prednisone exposure (PPE) on fetal kidney development remains unclear. In this study, pregnant mice were administered prednisone intragastrically during full-term pregnancy with different doses (0.25, 0.5, or 1 mg/(kg·day)), or at the dose of 1 mg/(kg·day) in different gestational days (GD) (GD0-9, GD10-18, or GD0-18). The pregnant mice were euthanized on GD18. HE staining revealed fetal kidney dysplasia, with an enlarged glomerular Bowman's capsule space and a reduced capillary network in the PPE groups. The expression of the podocyte and the mesangial cell marker genes was significantly reduced in the PPE groups. However, overall gene expression in renal tubules and collecting ducts were markedly increased. All of the above effects were more pronounced in high-dose, full-term pregnancy, and female fetuses. Studies on the mechanism of the female fetal kidney have revealed that PPE reduced the expression of Six2, increased the expression of Hnf1β, Hnf4α, and Wnt9b, and inhibited the expression of glial cell line-derived neurotrophic factor (GDNF) and Notch signaling pathways. In conclusion, this study demonstrated that there is a sex difference in the developmental toxicity of PPE to the fetal kidney, and the time effect is manifested as full-term pregnancy > early pregnancy > mid-late pregnancy.

2024-08-01·Poultry Science

Identification of key modules and hub genes involved in regulating the feather follicle development of Wannan chickens using WGCNA

Article

作者: Jiang, Runshen ; Xu, Jinmei ; Wang, Jiangxian ; Wei, Wei ; Xing, Chaohui ; Wang, Hao ; Zhang, Hong ; Guo, Xing ; Liu, Yanan

Carcass appearance is important economic trait, which affects customers in making purchase decisions. Both density and diameter of feather follicles are two important indicators of carcass appearance. However, the regulatory network and key genes be involved in feather follicle development remain poorly understood. To identify key genes and modules that involved in feather follicle development in chickens, 16 transcriptome datasets of Wannan chickens skin tissue (3 birds at the E9, E11, and E14, respectively, and 7 birds at the 12W) were used for weighted gene co-expression network analysis (WGCNA) analysis, and 12 skin tissue samples (3 birds for each stage) were selected for DEGs analysis. A total of 5,025, 2,337, and 10,623 DEGs were identified in 3 comparison groups, including the E9 vs. E11, the E11 vs. E14, and the E14 vs. 12W. Additionally, 31 co-expression gene modules were identified by WGCNA and the dark-orange, cyan, and blue module were found to be significantly associated with feather follicle development (p < 0.01). In total, 92,898 and 8,448 hub genes were obtained in the dark-orange, cyan, and blue modules, respectively. We focused on the cyan and blue modules, as 6 and 336 hub genes of these modules were identified to overlap with the DEGs of the three comparison groups, respectively. The 6 overlapped genes such as LAMC2, COL6A3, and COL6A2 etc., were over-represented in 12 categories such as focal adhesion and ECM-receptor interaction signaling pathway. Among the 336 genes that overlapped between the blue module and different DEGs comparison groups several genes including WNT7A and WNT9B were enriched in Wnt and ECM-receptor interaction signaling pathway. These results suggested that the LAMC2, COL6A3, COL6A2, WNT7A, and WNT9B genes may play a crucial role in the regulation of feather follicle development in Wannan chickens. Our results provided a reference for the molecular regulatory network and key genes in the development of feather follicles and contribute to molecular breeding for carcass appearance traits in chickens.

2024-06-01·iScience

RAD21 deficiency drives corneal to scleral differentiation fate switching via upregulating WNT9B

Article

作者: Zhou, Qingjun ; Chen, Yonglong ; Chu, Wai Kit ; Qi, Benxiang ; Liu, Hongyan ; Li, Zongyi ; Liu, Guanghui ; Duan, Haoyun ; Zhang, Bi Ning ; Shi, Zhaoying

The cornea and sclera are distinct adjacent tissues, yet their stromal cells originate from common neural crest cells (NCCs). Sclerocornea is a disease characterized by an indistinguishable boundary between the cornea and sclera. Previously, we identified a RAD21 mutation in a sclerocornea pedigree. Here, we investigated the impacts of RAD21 on NCC activities during eye development. RAD21 deficiency caused upregulation of PCDHGC3. Both RAD21 knockdown and PCDHGC3 upregulation disrupted the migration of NCCs. Transcriptome analysis indicated that WNT9B had 190.9-fold higher expression in scleral stroma than in corneal stroma. WNT9B was also significantly upregulated by both RAD21 knockdown and PCDHGC3 overexpression, and knock down of WNT9B rescued the differentiation and migration of NCCs with RAD21 deficiency. Consistently, overexpressing wnt9b in Xenopus tropicalis led to ocular developmental abnormalities. In summary, WNT9B is a determinant factor during NCC differentiation into corneal keratocytes or scleral stromal cells and is affected by RAD21 expression.

项与 WNT9B 相关的新闻（医药）

2023-10-20

·生物谷

Cell：李晓淳团队揭示Wnt生物发生和分泌以及Wnt7特异性信号的分子基础

该研究以Wnt7a的合成、分泌和激活入手，阐释了脂修饰的Wnt蛋白是如何在ER中完成由PORCN向WLS的转移，WLS如何在细胞表面释放Wnt，以及中枢神经中Wnt7 特异性共受体RECK是如何发挥功德克萨斯大学西南医学中心李晓淳实验室在 Cell 期刊发表了题为：Molecular basis of Wnt biogenesis, secretion and Wnt7 specific signaling 的研究论文【2】。该研究以Wnt7a的合成、分泌和激活入手，阐释了脂修饰的Wnt蛋白是如何在ER中完成由PORCN向WLS的转移，WLS如何在细胞表面释放Wnt，以及中枢神经中Wnt7 特异性共受体RECK是如何发挥功能的。为了鉴定ER中参与Wnt蛋白合成的因子，研究团队在HEK293细胞中共表达了Wnt7a-WLS-RECK复合物。电镜结构显示出一个未知内源性蛋白结合Wnt7a，质谱鉴定和AlphaFold结构预测指出该蛋白为钙网蛋白（calreticulin，CALR）。CALR的Lectin 结构域主要作用于Wnt7a 的第295位天冬酰胺糖基化修饰，此修饰位点在大部分Wnt中保守。当在Wnt7a或Wnt3a中突变掉该糖基化位点时，突变体丧失了与CALR的结合能力，同时分泌量减少，激活下游信号能力显著减弱。为了探究Wnt蛋白在被PORCN脂化时是否有CALR参与，研究团队共表达了PORCN和Wnt蛋白，CoIP实验显示，在Wnt蛋白存在的情况下，过表达的PORCN，内源WLS，内源CALR能够和Wnt蛋白形成四元复合物，加上对结构的分析，研究团队得出CALR通过稳定Wnt蛋白来帮助其从PORCN到WLS转运的结论。研究团队对其他18种Wnt蛋白进行氨基酸序列比对和CoIP实验，结果显示除了Wnt8a、Wnt8b、Wnt9a和Wnt9b，CALR参与其他15种Wnt的合成，揭示了CALR对于Wnt蛋白的折叠，转运和合成中具有重要作用。为了进一步探究Wnt蛋白是如何从WLS上释放的，研究团队又解析了单独的WLS结构。与Wnt7a-WLS复合物结构对比发现，复合物的WLS跨膜区间结合了一个磷脂分子，该结果与已经报道的Wnt8a-WLS结构（Cell 184:194）和Wnt3a-WLS结构（Nature Communications 12: 4541）类似。但是单独的WLS并没有结合磷脂分子，而且其跨膜区发生了显著的构像变化，使结合Wnt蛋白hairpin2和脂修饰的口袋闭合。另外，虽然磷脂分子没有直接参与和Wnt7a的互作，但是CoIP实验和分子动力学实验证明磷脂分子对于WLS结合Wnt7a非常重要，因此该研究首次提出由磷脂分子介导的Wnt从WLS释放模型。有趣的是，通过分析单独的WLS结构，他们发现WLS跨膜区存在一个空腔，可以作为其抑制剂的结合位点，抑制Wnt的分泌，为靶向WLS的药物设计提供了重要依据。此外，通过对Wnt7a-RECKCC4复合物结构的分析，作者发现作为Wnt7a的特异受体， RECK的CC4结构域结合在Wnt7a的N端结构域。参与RECK互作的氨基酸在其他17种Wnt蛋白里面是不保守的，突变二者相互作用的氨基酸会减弱Wnt7a介导的信号活性，从而揭示了RECK实现对Wnt7特异性的机理。 Wnt合成分泌以及Wnt7a信号通路示意图总而言之，这项工作通过结构生物学，生物化学和细胞生物学的方法鉴定了第一个Wnt合成中的伴侣蛋白，提出了Wnt合成和分泌的新模型，并且阐释了Wnt7共受体的作用。该研究为抗癌药物研发，中枢神经中血脑屏障修复提供了分子模型。

临床结果临床1期

2022-07-18

·生物谷

Hepatology: ALK1控制遗传性出血性肝毛细血管扩张症

该研究证实了肝内皮细胞ALK1信号保护器官特异性内皮细胞分化和血管分泌信号，防止血管畸形的发生。遗传性出血性毛细血管扩张症(HHT)是一种常染色体显性遗传病，可导致多器官血管畸形。HHT最常见的症状是鼻出血、毛细血管扩张和内脏损害。HHT的患病率较低，为1：5000，因此，诊断通常会延迟多年。复发性鼻出血影响约90%的HHT患者，是最常见和最明显的主诉。然而，肝脏等内部器官的畸形和分流与长期预后更相关，因为它们最终可能导致心力衰竭。在遗传性出血性毛细血管扩张症(HHT)中，严重的肝血管畸形与编码ALK1的激活素A受体样1型(ACVRL1)基因突变有关，ALK1是BMP9/BMP10的受体，调节血管发育。在这里，研究者建立了一种新的HHT小鼠模型，该模型只涉及肝脏，并具有足够的预期寿命，以研究ALK1信号在肝脏血管形成和代谢功能中的作用。图片来源: https://pubmed-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/35776660/ 近日，来自莱顿大学医学中心的研究者们在Hepatology杂志上发表了题为“ALK1 controls hepatic vessel formation, angiodiversity, and angiocrine functions in hereditary hemorrhagic telangiectasia of the liver”的文章，该研究证实了肝内皮细胞ALK1信号保护器官特异性内皮细胞分化和血管分泌信号，防止血管畸形的发生。长期存活的Alk1HEC-KO HHT模型为开发这种严重疾病的靶向治疗提供了新的机会。研究者将肝窦内皮细胞(LSEC)选择性Cre缺失品系Stab2-iCreF3与Acvrl1-Flobled小鼠杂交，获得LSEC特异性Acvrl1缺陷小鼠(Alk1HEC-KO)。Alk1HECKO小鼠表现出肝脏血管畸形和肝后血流增加，导致右室容量超负荷。转录学分析表明，在LSEC和中心静脉同一性的代价下，诱导了前血管生成/TIP细胞基因组和肝血管的动脉化。LSEC血管因子Wnt2、Wnt9b和Rspo3的缺失导致了Alk1HEC-KO小鼠和HHT患者肝脏标本中代谢肝区带的破坏。此外，在Alk1HEC-KO肝内皮细胞中，PrND和胎盘生长因子(PGF)表达上调，代表了HHT器官特异性发病的新候选基因。在LSEC体外，刺激或抑制ALK1信号反向调节DNA结合抑制物(ID)1-3，已知的Alk1转录靶点。对ALK1信号的刺激和对ID1-3功能的抑制证实了BMP9/ALK1/ID轴对WNT2和Rsp3的调节。机制总结图图片来源: https://pubmed-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/35776660/ 本研究的小鼠HHT模型与人类疾病之间的显著相似性证实了Alk1HEC-KO小鼠是研究HHT在肝脏中的发展以及在疾病发展的不同阶段开发和验证新的治疗策略的有价值的工具。在HHT晚期，由于肝脏分流和容量超负荷，心力衰竭是一种严重的并发症，这也反映在研究者HHT模型中。（生物谷 Bioon.com）参考文献 Christian David Schmid et al. ALK1 controls hepatic vessel formation, angiodiversity, and angiocrine functions in hereditary hemorrhagic telangiectasia of the liver. Hepatology. 2022 Jul 1. doi: 10.1002/hep.32641.