The Wnt antagonist and secreted frizzled-related protein 5: implications on lipid metabolism, inflammation, and type 2 diabetes mellitus

Liu, Lingbin; Chen, Xiao; Zhou, Xiangyu; Zhu, Qing

doi:10.1042/bsr20180011

Cited by 57 publications

(43 citation statements)

References 67 publications

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“…Previous studies confirmed that vascular insulin resistance in the arterioles of visceral adipose tissue in obese subjects is associated with upregulated Wnt5a-JNK signalling [14]. Secreted frizzled-related protein 5 (Sfrp5) has been shown to antagonize the Wnt/β-catenin signalling pathway, reducing β-cell insulin secretion by inhibiting the noncanonical Wnt signalling pathway [15].…”

Section: Introductionmentioning

confidence: 89%

Islet Stellate Cells Regulate Insulin Secretion via Wnt5a in Min6 Cells

Jones

Geng

et al. 2020

International Journal of Endocrinology

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Background. Type 2 diabetes mellitus is a serious public health problem worldwide. Accumulating evidence has shown that β-cell dysfunction is an important mechanism underlying diabetes mellitus. e changes in the physiological state of islet stellate cells (ISCs) and the effects of these cells on β cell function play an important role in the development of diabetes. is study aimed at elucidating the mechanism by which ISCs regulate insulin secretion from Min6 cells via the Wnt5a protein. Methods. Glucosestimulated insulin secretion (GSIS) from Min6 cells was examined by estimating the insulin levels in response to high glucose challenge after culture with ISC supernatant or exogenous Wnt5a. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) analyses were used to observe changes in the β-catenin, receptor tyrosine kinase-like orphan receptor 2 (Ror2), Ca (2+)/calmodulin (CaM)-dependent protein kinase II (CamKII), forkhead box O1 (FoxO1), pancreatic and duodenal homeobox 1 (PDX1), glucose transporter 2 (Glut2), insulin, and Cask mRNA and protein levels in the Wnt and insulin secretory pathways. Flow cytometry was used to confirm the intracellular Ca 2+ concentration in Min6 cells. Results. We observed a significant increase in insulin secretion from Min6 cells cocultured in vitro with supernatant from db/m mouse ISCs compared to that from Min6 cells cocultured with supernatant from db/db mouse ISCs; e intracellular Ca 2+ concentration in Min6 cells increased in cultured in vitro with supernatant from db/m mouse ISCs and exogenous Wnt5a compared to that from control Min6 cells. Culture of Min6 cells with exogenous Wnt5a caused a significant increase in pCamKII, pFoxO1, PDX-1, and Glut2 levels compared to those in Min6 cells cultured alone; this treatment further decreased Ror2 and Cask expression but did not affect β-catenin expression. Conclusion. ISCs regulate insulin secretion from Min6 cells through the Wnt5a protein-induced Wntcalcium and FoxO1-PDX1-GLUT2-insulin signalling cascades.

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Section: Introductionmentioning

confidence: 89%

Islet Stellate Cells Regulate Insulin Secretion via Wnt5a in Min6 Cells

Jones

Geng

et al. 2020

International Journal of Endocrinology

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“…Currently, many studies provided the potential inhibitors of the Wnt signaling pathway. The major inhibitors for the Wnt signal pathway include Dickkopf-1 (DKK-1) ( 30 , 31 ), Frizzled-related protein (sFRP) ( 32 – 34 ), Wnt inhibitory factor-1 (WIF-1) ( 31 , 35 , 36 ), Ceberus (CER) ( 31 ), and salinomycin ( 37 ). These potential inhibitors for targeting the TDRKH-AS1 is worth to be constructed and evaluated in future studies.…”

Section: Discussionmentioning

confidence: 99%

Long Non-coding RNA TDRKH-AS1 Promotes Colorectal Cancer Cell Proliferation and Invasion Through the β-Catenin Activated Wnt Signaling Pathway

et al. 2020

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Colorectal cancer (CRC) is a common cancer worldwide, with a lower 5-years survival rate. Recently, long non-coding RNAs (lncRNAs) have been well-studied as the oncogenes or the tumor suppressors in multiple malignancies, including CRC. However, their biological functions and potential mechanisms in human cancer remain unclear. Here, we evaluated the expression of TDRKH-AS1 in CRC tissues and identified its potential targets. We found that TDRKH-AS1 is upregulated in majority of CRC patients, which is also significantly correlated with their malignant characteristics and their dismal prognoses. The high expression of TDRKH-AS1 can promote cancer cell proliferation substantially and invasion based on in vitro experiments. We also recognized that the TDRKH-AS1 targets the β-catenin in the Wnt signaling pathway to exert its carcinogenic activity. TDRKH-AS1 could serve as a promising prognostic predictor and a potential therapeutic target for further early diagnoses and treatments via a non-invasive method.

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“…Other genes that are key regulators of lipid metabolism such as SCD, ACACA, FABP4, SFRP1, THRSP or the hub genes SFRP5 and FASN (Additional file 9: Table S9), also clustered in a tight co-expression module and they were significantly associated with linoleic and arachidonic fatty acids content in the gluteus medius muscle (Additional file 14: Table S14). The SFRP5 protein has been thoroughly studied as a central regulator of lipid accumulation and adipocytes differentiation, which are a result of an increased mitochondrial respiration promoted by SFRP5 blocking of Wnt signaling, hence repressing Wnt-induced oxidative metabolism [102]. The other identified SFRP element (SFRP1) has also been reported to be located in a genomic region overlapping a QTL for meat marbling [103,104].…”

Section: Weighted Co-expression Analyses Revealed Hub Genes Related Wmentioning

confidence: 99%

Co-expression network analysis predicts a key role of microRNAs in the adaptation of the porcine skeletal muscle to nutrient supply

Mármol-Sánchez

Ramayo-Caldas

Quintanilla

et al. 2020

J Animal Sci Biotechnol

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Background: The role of non-coding RNAs in the porcine muscle metabolism is poorly understood, with few studies investigating their expression patterns in response to nutrient supply. Therefore, we aimed to investigate the changes in microRNAs (miRNAs), long intergenic non-coding RNAs (lincRNAs) and mRNAs muscle expression before and after food intake. Results: We measured the miRNA, lincRNA and mRNA expression levels in the gluteus medius muscle of 12 gilts in a fasting condition (AL-T0) and 24 gilts fed ad libitum during either 5 h. (AL-T1, N = 12) or 7 h. (AL-T2, N = 12) prior to slaughter. The small RNA fraction was extracted from muscle samples retrieved from the 36 gilts and sequenced, whereas lincRNA and mRNA expression data were already available. In terms of mean and variance, the expression profiles of miRNAs and lincRNAs in the porcine muscle were quite different than those of mRNAs. Food intake induced the differential expression of 149 (AL-T0/AL-T1) and 435 (AL-T0/AL-T2) mRNAs, 6 (AL-T0/AL-T1) and 28 (AL-T0/AL-T2) miRNAs and none lincRNAs, while the number of differentially dispersed genes was much lower. Among the set of differentially expressed miRNAs, we identified ssc-miR-148a-3p, ssc-miR-22-3p and ssc-miR-1, which play key roles in the regulation of glucose and lipid metabolism. Besides, co-expression network analyses revealed several miRNAs that putatively interact with mRNAs playing key metabolic roles and that also showed differential expression before and after feeding. One case example was represented by seven miRNAs (ssc-miR-148a-3p, ssc-miR-151-3p, ssc-miR-30a-3p, ssc-miR-30e-3p, ssc-miR-421-5p, ssc-miR-493-5p and ssc-miR-503) which putatively interact with the PDK4 mRNA, one of the master regulators of glucose utilization and fatty acid oxidation. Conclusions: As a whole, our results evidence that microRNAs are likely to play an important role in the porcine skeletal muscle metabolic adaptation to nutrient availability.

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The Wnt antagonist and secreted frizzled-related protein 5: implications on lipid metabolism, inflammation, and type 2 diabetes mellitus

Cited by 57 publications

References 67 publications

Islet Stellate Cells Regulate Insulin Secretion via Wnt5a in Min6 Cells

Islet Stellate Cells Regulate Insulin Secretion via Wnt5a in Min6 Cells

Long Non-coding RNA TDRKH-AS1 Promotes Colorectal Cancer Cell Proliferation and Invasion Through the β-Catenin Activated Wnt Signaling Pathway

Co-expression network analysis predicts a key role of microRNAs in the adaptation of the porcine skeletal muscle to nutrient supply

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