Ask about this productRelated genes to: FZD5 Blocking Peptide
- Gene:
- FZD5 NIH gene
- Name:
- frizzled class receptor 5
- Previous symbol:
- C2orf31
- Synonyms:
- HFZ5, DKFZP434E2135
- Chromosome:
- 2q33.3
- Locus Type:
- gene with protein product
- Date approved:
- 1998-09-17
- Date modifiied:
- 2015-09-11
Related products to: FZD5 Blocking Peptide
Related articles to: FZD5 Blocking Peptide
- is an obligately intracellular bacterium that repurposes multiple cellular signaling pathways, including Wnt, Hippo, Notch, and Hedgehog to evade innate immune defenses of mononuclear phagocytes. Although noncanonical Wnt signaling activation by induces nuclear factor of activated T-cells (NFAT) activity, the functional consequences of this response have remained unclear. Here, we demonstrate that exploits noncanonical Wnt/Ca signaling to selectively activate NFATc1 and drive monocyte chemotactic chemokine production. In infected THP-1 cells, NFATc1 was exclusively activated, which was recapitulated in cells treated with soluble recombinant TRP120 (rTRP120) or TRP120 Wnt ligand short linear motif (SLiM) peptide (QDVASH). Correspondingly, significant increases and similar chemokine expression profiles were detected in THP-1 cells infected with or treated with soluble rTRP120. Moreover, treatment with the NFATc1 peptide inhibitor (11R-VIVIT) significantly inhibited NFAT activation and chemokine expression. Consistent with a requirement for Wnt signaling, Frizzled 5 (FZD5)-deficient THP-1 cells exhibited reduced NFATc1 activation and diminished chemokine production and monocyte recruitment. Although the TRP120 Wnt ligand SLiM phenocopied induced NFATc1 activation, it was insufficient to independently stimulate chemokine production. In contrast, ectopic expression of TRP120-induced chemokine expression, which was further amplified by TRP120 Wnt SLiM treatment, indicating both TRP120-directed extracellular Wnt signaling and intracellular mechanisms are required. Collectively, these findings define a previously unrecognized pathogen-driven strategy that co-opts non-canonical Wnt/NFAT signaling to promote monocyte chemotactic chemokine production.IMPORTANCE is an obligately intracellular bacterium that causes human monocytic ehrlichiosis and survives within mononuclear phagocytes by manipulating key cell signaling pathways. Unlike most Gram-negative bacteria, lacks classical pathogen-associated molecular patterns such as lipopolysaccharide and peptidoglycan, yet it stimulates strong chemokine production during infection; however, the molecular patterns, receptors and signaling pathways involved in inducing chemokine expression are unknown. Here, we uncover a cell signaling strategy whereby , through TRP120 Wnt ligand mimicry, co-opts the noncanonical Wnt/Ca signaling to selectively activate NFATc1 and drive chemokine expression. This pathogen-driven NFAT activation promotes monocyte recruitment, revealing a previously unrecognized chemokine induction mechanism. - Source: PubMed
Publication date: 2026/06/22
Solomon Regina NBui Duc-CuongPai Ayana PMcBride Jere W - Two hundred Holstein dairy cows (milk yield of 34.5 ± 0.6 kg/d, 3.1 ± 1.2 lactations) were enrolled to investigate the role of WNTs signaling network in early pregnancy loss. The ISG15 mRNA abundance of uterine luminal cells obtained via brushing on day 16 after service was used to determine initial pregnancy status, with confirmation via ultrasound on days 32 and 60. The mRNA abundance of cells obtained from uterine brushing for WNT2, WNT5A, WNT7A, WNT11, frizzled receptors (FZD), dickkopf proteins (DKK1), Kremen and LDL receptor related protein (LRP 5/6), lymphoid enhancer-binding factor 1 (LEF1) and transcription factor 7 (TCF) was determined at day16 after insemination. Relative mRNA abundance of DKK1 (1.98-fold), WNT5A (2.67-fold), WNT7A (1.83-fold) and WNT11 (2.16-fold) genes in pregnant cows were significantly greater than in cows with early embryonic mortality (P < 0.05). In contrast, relative mRNA abundance of WNT2 (3.35-fold) and FZD6 (5.50-fold) genes were significantly greater in pregnant-embryo loss cows compared to pregnant cows on day 16 (P < 0.05). The relative mRNA abundance of LRP5, LRP6, LEF1, FZD3, FZD5, FZD8 and TCF genes were not affected by pregnancy status although their variances were lower; however, there was a negative correlation among ISG15 and these genes. In conclusion, differences in mRNA abundance of WNT signaling genes in uterine brushing samples are associated with pregnancy status in lactating dairy cows and may contribute to minimizing early bovine pregnancy losses. - Source: PubMed
Publication date: 2026/06/04
Dirandeh EAnsari-Pirsaraei ZThatcher W W - Macrocyclization is a powerful strategy to enhance the conformational control and functional potential of peptide drug candidates. Embedding such architectures within genetically encoded display platforms enables the discovery of peptides predisposed toward bioactive conformations, thereby streamlining downstream development. Here, we integrate tetrafunctional scaffolds into mRNA display to enable the direct discovery of tricyclic peptides through orthogonal reactions with cysteine and azidohomoalanine residues. Scaffold rotational flexibility resolves the topological challenge by yielding a single, well-defined tricyclic architecture. Using this approach, we discover tricyclic peptides against an antibody and the Fzd5 receptor as model targets, with our best hits having low nanomolar affinity and minimal degradation in serum after 24 h, and also demonstrate target engagement in cell culture. This approach thus has the potential to accelerate peptide drug discovery through the direct generation of advanced multicyclic hits. - Source: PubMed
Publication date: 2026/05/28
Liu MinglongThijssen VitoVerhoork Sanne J MKale Sangram SGoldflam MichaelTimmerman PeterJongkees Seino A K - Major depressive disorder (MDD) is a prevalent mental illness, and inflammatory processes are considered a pivotal component of the pathogenesis of MDD. This study aims to identify novel biomarkers associated with the development of MDD and to elucidate the underlying immunological mechanisms. - Source: PubMed
Publication date: 2026/04/30
Wu XinyuZhou ShaomingYang PingChen JiayiLiu HonghuaShi LuZhang Xuehua - Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease driven by persistent activation of pulmonary myofibroblasts, but the regulatory mechanisms sustaining this pathological state remain incompletely understood. Using single-cell RNA sequencing (scRNA-seq), we identified SFRP2 (secreted frizzled related protein 2) as a critical mediator of profibrotic myofibroblasts in IPF lungs. Functional studies revealed that SFRP2 acted in an autocrine manner to promote myofibroblast activation and extracellular matrix (ECM) production. Mechanistically, SFRP2 activated FZD5-mediated non-canonical WNT-Ca signaling, leading to PPP3/calcineurin-dependent translocation of PINK1 from the outer to the inner mitochondrial membrane (IMM), where it was degraded, thereby inhibiting PINK1-mediated mitophagy. Furthermore, therapeutic intervention with AAV6-sh, SFRP2-neutralizing antibody, or the autophagy inducer rapamycin significantly ameliorated lung fibrosis in bleomycin (BLM)-induced mouse models. Our results define a novel autocrine SFRP2-mitophagy regulatory axis that perpetuates myofibroblast activation and represents a promising therapeutic target for pulmonary fibrosis.: AAV: adeno-associated virus; BLM: bleomycin; CQ: chloroquine; ECM: extracellular matrix; FZD5: frizzled class receptor 5; H&E: hematoxylin and eosin; IHC: immunohistochemical; IMM: inner mitochondrial membrane; IPF: idiopathic pulmonary fibrosis; Micro-CT: micro-computed tomography; mtROS: mitochondrial reactive oxygen species; PMLFs: primary mouse lung fibroblasts; qPCR: quantitative real-time PCR; scRNA-seq: single-cell RNA sequencing; SFRP2: secreted frizzled related protein 2; TEM: transmission electron microscopy; ∆Ψm: mitochondrial membrane potential. - Source: PubMed
Publication date: 2026/03/15
Lin YingyingLei TianxiangJia YifanYao MeilingWang XiaofengHuang ShaojieWang ZhongxingLai Xiaofan