Secreted frizzled-related protein 5: A promising therapeutic target for metabolic diseases via regulation of Wnt signaling

Song, Yi; Ma, Yanhui; Zhang, Kexin; Zhang, Wenqiang; Xiong, Gang; Qi, Tongbing; Shi, Junfeng; Qiu, Hongyan; Zhang, Jingwen; Han, Fangfang; Kan, Chengxia; Sun, Xiaodong

doi:10.1016/j.bbrc.2023.08.008

Cited by 4 publications

(9 citation statements)

References 103 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More research is needed to determine the specific role of cSFRP5 in shaping the tumour immune cell microenvironment in CRC. SFRP5 has garnered attention as a promising therapeutic target for various conditions, including metabolic diseases 16 . Notably, SFRP5 administration reversed hyperglycaemia and hepatic steatosis in multiple mouse models of metabolic dysfunction 12 .…”

Section: Discussionmentioning

confidence: 99%

“…In humans, downregulation of SFRP5 contributes to proinflammatory conditions in visceral adipose tissue, potentially exacerbating obesity-related comorbidities 15 . Indeed, circulating SFRP5 (cSFRP5) has emerged as a potential biomarker in various diseases, participating in diverse pathological processes [16][17][18] . Typically, individuals with metabolic disorders like obesity, insulin resistance, and diabetes exhibit reduced levels of cSFRP5 compared to healthy controls [16][17][18][19] .…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, circulating SFRP5 (cSFRP5) has emerged as a potential biomarker in various diseases, participating in diverse pathological processes 16–18 . Typically, individuals with metabolic disorders like obesity, insulin resistance, and diabetes exhibit reduced levels of cSFRP5 compared to healthy controls 16–19 .…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, circulating SFRP5 (cSFRP5) has emerged as a potential biomarker in various diseases, participating in diverse pathological processes [16][17][18] . Typically, individuals with metabolic disorders like obesity, insulin resistance, and diabetes exhibit reduced levels of cSFRP5 compared to healthy controls [16][17][18][19] . Meanwhile, interventions leading to significant weight loss in overweight individuals are associated with increased cSFRP5 levels, further highlighting its role in metabolic regulation [20][21][22] .…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Circulating SFRP5 levels are elevated in colorectal cancer and correlate with overall survival in stage II-III disease

Li,

Liu,

Yeo

et al. 2024

Preprint

View full text Add to dashboard Cite

Secreted Frizzled-Related Protein 5 (SFRP5) modulates Wnt signalling pathways, affecting diverse biological processes. We assessed the diagnostic and prognostic value of circulating SFRP5 (cSFRP5) in colorectal cancer (CRC). Plasma cSFRP5 concentrations were measured using ELISA in healthy donors (n=133), individuals diagnosed with CRC (n=449), colorectal polyps (n=85), and medical conditions in other organs including cancer, inflammation, and benign states (n=64). Patients with CRC, polyps, and other conditions showed higher cSFRP5 levels than healthy individuals (p<0.0001). Receiver operating characteristic curves comparing healthy donors with medical conditions, polyps, and CRC were 0.814 (p<0.0001), 0.763 (p<0.0001), and 0.762 (p<0.0001), respectively. In CRC, cSFRP5 correlated with patient age (p<0.0001), tumour stage (p<0.0001), and histological differentiation (p=0.0273). Levels peaked in stage II versus I (p<0.0001), III (p=0.0007), or IV (p<0.0001), and were higher in stage III versus I (p=0.0007) and IV (p=0.0054), with no difference between I and IV. Elevated cSFRP5 levels predicted longer overall survival in stage II-III CRC (univariate: HR 1.82, 95% CI 1.02-3.26, p=0.024; multivariable: HR 2.34, 95% CI 1.12-4.88, p=0.015). This study confirms elevated cSFRP5 levels in CRC and reveals a correlation between elevated cSFRP5 and overall survival in stage II-III disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Circulating SFRP5 levels are elevated in colorectal cancer and correlate with overall survival in stage II-III disease

Li,

Liu,

Yeo

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…15 Indeed, circulating SFRP5 (cSFRP5) has emerged as a potential biomarker in various diseases, participating in diverse pathological processes. [16][17][18] Typically, individuals with metabolic disorders like obesity, insulin resistance, and diabetes exhibit reduced levels of cSFRP5 compared to healthy controls. [16][17][18][19] Meanwhile, interventions leading to significant weight loss in overweight individuals are associated with increased cSFRP5 levels, further highlighting its role in metabolic regulation.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic and prognostic significance of circulating secreted frizzled‐related protein 5 in colorectal cancer

Li,

Liu,

Yeo

et al. 2024

Cancer Medicine

View full text Add to dashboard Cite

BackgroundSecreted Frizzled‐Related Protein 5 (SFRP5) modulates Wnt signalling pathways, affecting diverse biological processes. We assessed the diagnostic and prognostic value of circulating SFRP5 (cSFRP5) in colorectal cancer (CRC)MethodsPlasma cSFRP5 concentrations were measured using enzyme‐linked immunosorbent assay (ELISA) in healthy donors (n = 133), individuals diagnosed with CRC (n = 449), colorectal polyps (n = 85), and medical conditions in other organs including cancer, inflammation, and benign states (n = 64).ResultsPatients with CRC, polyps, and other conditions showed higher cSFRP5 levels than healthy individuals (p < 0.0001). Receiver operating characteristic curves comparing healthy donors with medical conditions, polyps and CRC were 0.814 (p < 0.0001), 0.763 (p < 0.0001) and 0.762 (p < 0.0001), respectively. In CRC, cSFRP5 correlated with patient age (p < 0.0001), tumour stage (p < 0.0001), and histological differentiation (p = 0.0273). Levels, adjusted for patient age, sex, plasma age and collection institution, peaked in stage II versus I (p < 0.0001), III (p = 0.0002) and IV (p < 0.0001), were lowest in stage I versus III (p = 0.0002) and IV (p = 0.0413), with no difference between stage III and IV. Elevated cSFRP5 levels predicted longer overall survival in stages II‐III CRC (univariate: HR 1.82, 95% CI: 1.02–3.26, p = 0.024; multivariable: HR 2.34, 95% CI: 1.12–4.88, p = 0.015).ConclusionThis study confirms cSFRP5 levels are elevated in CRC compared to healthy control and reveals a correlation between elevated cSFRP5 and overall survival in stages II‐III disease.

show abstract

Chondroprotective functions of neutrophil-derived extracellular vesicles by promoting the production of secreted frizzled-related protein 5 in cartilage

Kitahara,

Ebata,

Liyile

et al. 2024

Cell Commun Signal

View full text Add to dashboard Cite

Background Osteoarthritis (OA) is the most common degenerative joint disease characterized by cartilage degradation and various degrees of inflammation in the synovium. Growing evidence highlights that neutrophil extracellular vesicles (EVs) play a protective role in arthritic joints by promoting the resolution of inflammation and the synthesis of proteoglycans in cartilage. However, this homeostatic function is dependent on the activation state of neutrophils and the surrounding environment/tissues. Hence, we explored the chondroprotective functions of neutrophil-derived EVs under different stimulation conditions and the underlying molecular mechanism. Methods Human blood-derived neutrophils, murine bone marrow-derived neutrophils, C-28I2 cells and primary chondrocytes were used. Neutrophils were stimulated with different cytokines, and their EVs were isolated for chondrocyte stimulation and further subjected to RNA-sequencing analysis. Two experimental murine OA models were used, and the treatment was performed by intraarticular injections. Results Conditioned medium from neutrophils stimulated with TGF-β (N-β) had the greatest inhibitory effect on the expression of catabolic factors in stimulated chondrocytes. These protective effects were not impaired when conditioned medium of N-β from AnxA1 -deficient mice was used. Consistent with these results, EVs isolated from N-β significantly reduced the expression of catabolic factors in stimulated chondrocytes. Bulk RNA-seq analysis revealed that secreted frizzled-related protein 5 (SFRP5) is upregulated in N-β-EV-stimulated chondrocytes. Furthermore, recombinant SFRP5 treatment significantly reduced the expression of catabolic factors in vitro and catabolic process in experimental murine OA models. Conclusions The current study emphasizes the potential therapeutic application of neutrophils in OA and provides new knowledge on the molecular mechanisms underlying their function. Supplementary Information The online version contains supplementary material available at 10.1186/s12964-024-01953-8.

show abstract

Secreted frizzled-related protein 5: A promising therapeutic target for metabolic diseases via regulation of Wnt signaling

Cited by 4 publications

References 103 publications

Circulating SFRP5 levels are elevated in colorectal cancer and correlate with overall survival in stage II-III disease

Circulating SFRP5 levels are elevated in colorectal cancer and correlate with overall survival in stage II-III disease

Diagnostic and prognostic significance of circulating secreted frizzled‐related protein 5 in colorectal cancer

Chondroprotective functions of neutrophil-derived extracellular vesicles by promoting the production of secreted frizzled-related protein 5 in cartilage

Contact Info

Product

Resources

About