Follistatin-like 1 (FSTL1) interacts with Wnt ligands and Frizzled receptors to enhance Wnt/β-catenin signaling in obstructed kidneys in vivo

Wang, Yan; Zheng, Gaofeng; Liu, Yang; Li, Jinhong; Huang, Huihui; Xu, Chunhua; Zeng, Yelin; Zhang, Xiaoyi; Qin, Jinzhong; Dai, Chunsun; Hambrock, Harald O.; Hartmann, Ursula; Feng, Bo; Mak, Kin Cheung; Liu, Youhua; Lan, Hui‐Yao; Huang, Yü; Zheng, Zhihua; Xia, Yin

doi:10.1016/j.jbc.2022.102010

Cited by 18 publications

(11 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The high expression of SPARC in liver cancer and bladder cancer may inhibit apoptosis of tumor cells through the PI3K/AKT signaling pathway, while promoting the proliferation, invasion and metastasis of tumor cells. SPARC is an upregulated gene in CHD1L-induced hepatocellular carcinoma (8)(9)(10)(11). In human NSCLC cells expressing SPARC induced by TGF-β, the expression of CDH1 did not change, while SPARC was strongly expressed in metastatic NSCLC.…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of SPARC expression in non‑small cell lung cancer: A meta‑analysis and bioinformatics analysis

Shi

Zhang

et al. 2022

Oncol Lett

View full text Add to dashboard Cite

The aim of the present study was to elucidate the significance of secreted protein acidic and cysteine rich (SPARC) expression in non-small cell lung cancer (NSCLC) in terms of clinicopathology, immune-cell infiltration and survival prognosis. A meta-analysis and bioinformatics analysis were performed using studies retrieved with PubMed, Web of Science, Wanfang Data and the Chinese National Knowledge Infrastructure databases. The meta-analysis suggested that, compared with normal tissues, SPARC expression was elevated in NSCLC tissues. The expression of SPARC was not significantly associated with TNM stage and lymph-node metastasis, and was positively associated with patient gender. Regarding the differential expression of SPARC and the relationship between expression levels and survival, the Oncomine database was consulted and Kaplan-Meier curves were drawn. It was indicated that SPARC mRNA expression levels were higher in NSCLC tissues than in normal tissues. Low expression of SPARC mRNA was negatively associated with overall survival, first progression survival and post-progression survival of patients. Further exploration of the relationship between SPARC expression and survival by univariate analysis indicated that TNM stage, lymph node metastasis, distant metastasis and depth of infiltration of lung cancer were negatively associated with patient prognosis. Cox multifactorial analysis suggested that SPARC expression levels and TNM stage were risk factors significantly affecting the prognosis of patients with NSCLC. Analysis with the GEPIA and UALCAN databases further indicated that the mRNA expression level of SPARC in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) was higher than that in normal lung tissue, and the SPARC expression levels were affected by factors such as the TNM stage of lung cancer.A lower the level of SPARC mRNA expression was associated with a better relative survival prognosis of patients. In the Human Protein Atlas database, the expression level of SPARC protein was higher in LUAD and LUSC than in normal lung tissue. In the Timer database, the expression level of SPARC was closely linked to immune cells related to the occurrence of lung cancer, and the degree of immune-cell infiltration and SPARC protein expression were closely related to the prognosis of patients with lung cancer. Immune cells were indicated to exhibit significant inhibition of DNA proliferation mutation mechanisms in lung cancer (P<0.05). In summary, SPARC expression may be used as a valuable indicator of prognosis in patients with NSCLC, which may provide new approaches for preventative treatment.

show abstract

Section: Introductionmentioning

confidence: 99%

Prognostic significance of SPARC expression in non‑small cell lung cancer: A meta‑analysis and bioinformatics analysis

Shi

Zhang

et al. 2022

Oncol Lett

View full text Add to dashboard Cite

show abstract

“…By activating nuclear factor-kappa B (NF-κB) and wingless (Wnt)/β-catenin pathways, FSTL1 has been found to promote the progression of different forms of CKD, including focal segmental glomerular sclerosis(FSGS), membranous nephropathy (MN), immunoglobulin A (IgA) nephropathy (IgAN), etc. ( 19 , 20 ). In the present study, the expression level of FSTL1 in the renal tubules of DKD individuals was increased in both test and validation sets and displayed a positive correlation with the serum creatinine level of patients and a negative correlation with GFR levels.…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of immune and cuproptosis - related genes for diabetic nephropathy by WGCNA and machine learning

Chen,

Liao,

Wang

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

BackgroundAs the leading cause of chronic kidney disease, diabetic kidney disease (DKD) is an enormous burden for all healthcare systems around the world. However, its early diagnosis has no effective methods.MethodsFirst, gene expression data in GEO database were extracted, and the differential genes of diabetic tubulopathy were obtained. Immune-related genesets were generated by WGCNA and immune cell infiltration analyses. Then, differentially expressed immune-related cuproptosis genes (DEICGs) were derived by the intersection of differential genes and genes related to cuproptosis and immune. To investigate the functions of DEICGs, volcano plots and GO term enrichment analysis was performed. Machine learning and protein-protein interaction (PPI) network analysis helped to finally screen out hub genes. The diagnostic efficacy of them was evaluated by GSEA analysis, receiver operating characteristic (ROC) curve, single-cell RNA sequencing and the Nephroseq website. The expression of hub genes at the animal level by STZ -induced and db/db DKD mouse models was further verified.ResultsFinally, three hub genes, including FSTL1, CX3CR1 and AGR2 that were up-regulated in both the test set GSE30122 and the validation set GSE30529, were screened. The areas under the curve (AUCs) of ROC curves of hub genes were 0.911, 0.935 and 0.922, respectively, and 0.946 when taking as a whole. Correlation analysis showed that the expression level of three hub genes demonstrated their negative relationship with GFR, while those of FSTL1 displayed a positive correlation with the level of serum creatinine. GSEA was enriched in inflammatory and immune-related pathways. Single-nucleus RNA sequencing indicated the main distribution of FSTL1 in podocyte and mesangial cells, the high expression of CX3CR1 in leukocytes and the main localization of AGR2 in the loop of Henle. In mouse models, all three hub genes were increased in both STZ-induced and db/db DKD models.ConclusionMachine learning was combined with WGCNA, immune cell infiltration and PPI analyses to identify three hub genes associated with cuproptosis, immunity and diabetic nephropathy, which all have great potential as diagnostic markers for DKD and even predict disease progression.

show abstract

“…According to our findings, under grade II or III glioma conditions, the function of DKK3 to suppress Wnt/β-catenin signaling seems to be somewhat inhibited. Furthermore, based on our findings, DKK3 may positively interact with FSTL1, which is known to activate the Wnt/β-catenin pathway and is involved in tumorigenesis [ 35 , 36 ]. This may activate the Wnt/β-catenin signaling pathway in grade II or III glioma, leading to glioma proliferation.…”

Section: Discussionmentioning

confidence: 99%

DKK3 expression is associated with immunosuppression and poor prognosis in glioblastoma, in contrast to lower-grade gliomas

et al. 2023

View full text Add to dashboard Cite

Purpose We previously reported that expression of dickkopf-3 (DKK3), which is involved in the Wnt/β-catenin pathway, is significantly associated with prognosis in patients with glioblastoma multiforme (GBM). The aim of this study was to compare the association of DKK3 with other Wnt/β-catenin pathway-related genes and immune responses between lower grade glioma (LGG) and GBM. Methods We obtained the clinicopathological data of 515 patients with LGG (World Health Organization [WHO] grade II and III glioma) and 525 patients with GBM from the Cancer Genome Atlas (TCGA) database. We performed Pearson’s correlation analysis to investigate the relationships between Wnt/β-catenin-related gene expression in LGG and GBM. Linear regression analysis was performed to identify the association between DKK3 expression and immune cell fractions in all grade II to IV gliomas. Results A total of 1,040 patients with WHO grade II to IV gliomas were included in the study. As the grade of glioma increased, DKK3 showed a tendency to be more strongly positively correlated with the expression of other Wnt/β-catenin pathway-related genes. DKK3 was not associated with immunosuppression in LGG but was associated with downregulation of immune responses in GBM. We hypothesized that the role of DKK3 in the Wnt/β-catenin pathway might be different between LGG and GBM. Conclusion According to our findings, DKK3 expression had a weak effect on LGG but a significant effect on immunosuppression and poor prognosis in GBM. Therefore, DKK3 expression seems to play different roles, through the Wnt/β-catenin pathway, between LGG and GBM.

show abstract

Follistatin-like 1 (FSTL1) interacts with Wnt ligands and Frizzled receptors to enhance Wnt/β-catenin signaling in obstructed kidneys in vivo

Cited by 18 publications

References 66 publications

Prognostic significance of SPARC expression in non‑small cell lung cancer: A meta‑analysis and bioinformatics analysis

Prognostic significance of SPARC expression in non‑small cell lung cancer: A meta‑analysis and bioinformatics analysis

Identification and validation of immune and cuproptosis - related genes for diabetic nephropathy by WGCNA and machine learning

DKK3 expression is associated with immunosuppression and poor prognosis in glioblastoma, in contrast to lower-grade gliomas

Contact Info

Product

Resources

About