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Last update 08 May 2025

SFRP4

Last update 08 May 2025

Basic Info

Synonyms

Frizzled protein, human endometrium, FRP-4, frpHE

+ [5]

Introduction

Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell types (By similarity). SFRP4 plays a role in bone morphogenesis. May also act as a regulator of adult uterine morphology and function. May also increase apoptosis during ovulation possibly through modulation of FZ1/FZ4/WNT4 signaling (By similarity). Has phosphaturic effects by specifically inhibiting sodium-dependent phosphate uptake (PubMed:12952927).

Drugs associated with SFRP4

HG-1097

Target

SFRP4

Mechanism

SFRP4 modulators

Active Org.-

Originator Org.

Human Genome Sciences, Inc.

Active Indication-

Inactive Indication

Neoplasms

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with SFRP4

100 Translational Medicine associated with SFRP4

0 Patents (Medical) associated with SFRP4

568

Literatures (Medical) associated with SFRP4

01 May 2025·Biochemical and Biophysical Research Communications

Effect of resveratrol and quercetin on SFRP4 as a biomarker of diabesity: In silico and in vivo studies

Article

Author: Rehman, Asim ; Bukhari, Shazia Anwer ; Noreen, Razia ; Chauhdary, Zunera ; Akhter, Naheed

The concurrent presence of complex metabolic disorders such as obesity and diabetes within an individual is known as diabesity. Various organs are involved in metabolic chronic diseases like obesity, hypertension, and diabetes. In the last few years, the rise in diabetes cases has coincided with the rapid elevation in obesity rates, resulting in a global health crisis. Major risk factors playing a critical role in the spread of obesity include high-fat food consumption, high-calorie foods, and insufficient physical activity. Diabetes is strongly linked with obesity in terms of metabolic abnormalities and physiological processes, including inflammation. Diabetes type 2 (T2D) is caused primarily by insulin resistance and insufficient insulin release from beta cells of the pancreas. An obese or overweight individual has a strong association with insulin resistance, which in turn leads to the development of T2D. Metabolic stress due to nutrient overload releases different types of inflammatory mediators (such as TNF-α, IL-6, and SFRP4) from adipose tissues in obesity. Secreted frizzled-related protein 4 (SFRP4) is also an inflammatory mediator that impairs insulin secretion. SFRP4 acts as an early biomarker for diabesity expressed with interleukin-1 beta (IL-1β) in the adipose tissues that hinders the exocytosis of insulin-secreting granules from the pancreatic β-cells and is a potential target for preserving β-cell dysfunction and the diabesity treatment. In the current study, plant-based phytocompounds were identified and investigated in silico and in vivo for their ability to suppress the expression of SFRP4. In a diet-induced mouse model, short-listed compounds such as resveratrol and quercetin at higher and lower doses were found effective and significant in reducing the anti-inflammatory mediators and SFRP4 levels. Overall, the current study describes the expression of SFRP4, IL-6, and TNF-α, and its inhibition by various inhibitors. Moreover, the study's findings suggest that resveratrol and quercetin hold promise as potential treatments for diabesity.

04 Apr 2025·Medicine

Screening and identification analysis of core markers for leukemia and cervical cancer: Calmodulin 3 as a core target

Article

Author: Zhu, Xiaoqing ; Shao, Danfeng ; Yu, Huaiying

Leukemia is a type of malignant tumor affecting hematopoietic system. Cervical cancer is a malignant tumor of female reproductive tract. The relationship between Calmodulin 3 (CALM3) and leukemia, cervical cancer remains unclear. Leukemia dataset GSE26294 and cervical cancer dataset GSE173097 profiles were downloaded from gene expression omnibus. Principal component analysis, differentially expressed genes (DEGs) screening, weighted gene co-expression network analysis (WGCNA), functional enrichment analysis, gene set enrichment analysis, immune infiltration analysis, protein–protein interaction network construction and analysis, survival analysis were performed. Gene expression heatmaps were plotted. Comparative Toxicogenomics Database (CTD) was used to find diseases most related to core genes. 77 DEGs were identified. According to gene ontology, in biological process category, they were mainly enriched in cell proliferation, immune response, and apoptotic process. In cellular component category, they were mainly enriched in nucleus and Golgi apparatus. In molecular function category, they were mainly enriched in DNA binding, protein binding, transcription factor activity. In Kyoto encyclopedia of gene and genome analysis, they were mainly enriched in cell adhesion molecules, Wnt signaling pathway, cAMP signaling pathway, cGMP-PKG signaling pathway, and basal cell carcinoma. The soft-threshold power in WGCNA was set to 1, generating 6 modules. Finally identifying 3 core genes (CALM3, secreted frizzled-related protein 4, plasminogen). CTD analysis revealed that core genes were related to leukemia, coagulation disorders, vaginal tumors, cervical tumors, autoimmune diseases, and inflammation. CALM3 is lowly expressed in leukemia samples and highly expressed in cervical cancer samples.

01 Mar 2025·Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

A novel function of the Wnt antagonist secreted frizzled-related protein 4 as a transcriptional regulator of Dickkopf-1, another Wnt antagonist, in glioblastoma cell line U87MG

Article

Author: Warrier, Sudha ; Dharmarajan, Arun ; Yasmin, Ishmat Ara

Wnt/β-catenin pathway dysregulation is associated with glioblastoma multiforme (GBM) pathogenesis and Wnt antagonists are downregulated in GBM. Wnt antagonist secreted frizzled-related protein 4 (sFRP4) has a tissue-specific, anti-metastatic and anti-stemness property. Our lab previously reported that gene silencing of sFRP4 in GBM cell line U87MG increases expression of another Wnt antagonist, Dickkopf-1 (Dkk1) and sFRP4 has a DNA binding ability. These findings in accordance with the nuclear localization of sFRP4 led to our present hypothesis that sFRP4 presumably negatively regulates Dkk1 and it probably interacts with the promoter region of Dkk1. Methylation-specific PCR (MSP), chromatin accessibility real-time PCR (ChART-PCR) assay, chromatin immunoprecipitation (ChIP), and quantitative DNA-protein interaction enzyme-linked immunosorbent assay (qDPI-ELISA) were carried out to test our hypothesis. We demonstrated that sFRP4 overexpression does not alter the methylation status of the Dkk1 promoter region. sFRP4 overexpression inhibits DNA-transcription factor interaction and enables chromatin accessibility to DNase I. Pertinently, sFRP4 has strong putative binding sites in the Dkk1 promoter region and its overexpression disrupts its interaction with the Dkk1 promoter. Interestingly, sFRP4 has the strongest affinity towards the -282 to +118 bp region. Downregulation of Dkk1 by overexpressed sFRP4 occurs by inhibition of the direct interaction of sFRP4 with the promoter region of Dkk1 as observed with low concentrations of sFRP4. We report for the first time a novel function of the Wnt antagonist sFRP4 acting as a transcription factor for another Wnt antagonist Dkk1, throwing open a new vista in the complex interplay between different antagonists of the Wnt pathway.

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SFRP4

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