Novel roles of Tsukushi in signaling pathways and multiple disease processes

Deng, Xia; Li, Yanyan; Guo, Chen; Zhao, Zhicong; Yuan, Guoyue

doi:10.1002/biof.1723

Cited by 9 publications

(5 citation statements)

References 51 publications

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“…The B2 receptor is associated with G proteins that stimulate a phosphatidylinositol–calcium second messenger system [ 12 ]. TSKU encodes a small leucine-rich proteoglycan and has been predicted or partially demonstrated to be involved in animal organ development, cholesterol homeostasis, bone formation [ 13 ], and glycolipid metabolism [ 14 ]; however, little is known about its exact functions.…”

Section: Resultsmentioning

confidence: 99%

Isolation of Reporter Cells That Respond to Vitamin A and/or D Using a piggyBac Transposon Promoter-Trapping Vector System

Ishikawa

Tamamura

Takahashi

et al. 2022

IJMS

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Previously, we established a highly sensitive promoter-trapping vector system using the piggyBac transposon for the efficient isolation of reporter cells. Herein, we examine whether this screening system can be applied to obtain vitamin-responsive cells. As a result, one and two reporter cells that responded to bexarotene (vitamin A) and calcitriol (vitamin D), respectively, were isolated from 4.7 × 106 seeded HeLaS3 cells. 5′ RACE analyses identified the well-known CYP24A1 gene as a calcitriol-responsive gene, as well as two new bexarotene- or calcitriol-responsive genes, BDKRB2 and TSKU, respectively. TSKU, interestingly, also responded to bexarotene. Endogenous levels of the TSKU and BDKRB2 transcripts displayed only slight changes and were not detected in the comprehensive analyses performed to date. Dose–response analyses of BDKRB2 and TSKU reporter cells in parallel revealed a differential profile in response to each vitamin A agonist, suggesting a bioanalyzer. The present study demonstrates that producing multiple reporter cells by a type of random screening can efficiently identify novel genes with unusual characteristics and be used for the profiling of the properties of vitamin compounds. Similar approaches to the method shown here may be useful for identifying new markers and for the analysis or diagnosis of nutrients, toxins, metabolites, etc.

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Section: Resultsmentioning

confidence: 99%

Isolation of Reporter Cells That Respond to Vitamin A and/or D Using a piggyBac Transposon Promoter-Trapping Vector System

Ishikawa

Tamamura

Takahashi

et al. 2022

IJMS

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“…It has been shown that hepatic TSK acutely modulates gene expression in the mouse liver [ 5 ], indicating that TSK acts, at least, via an autocrine and/or paracrine mechanism. TSK is an extracellular protein that can locally affect the activity of several signaling pathways in chicks and Xenopus [ 3 , 4 ]. TSK may directly bind to a still unidentified membrane receptor, or even interact with proteins in the plasma to modulate their functions.…”

Section: Discussionmentioning

confidence: 99%

“…TSK was originally identified in the lens of chicks, and this molecule was named after its expression pattern in chick embryos, which is similar to the shape of the Japanese horsetail plant, Tsukushi [ 2 ]. TSK has been shown to be associated with various physiological processes, including growth and development, wound healing, and cartilage formation [ 3 ]. Studies in chicks and Xenopus showed that TSK controls different signaling pathways, including bone morphogenetic protein, β-catenin/Wnt, mitogen-activated protein kinase/fibroblast growth factor and transforming growth factor-β signaling pathways, during development and organogenesis, by interacting with various soluble factors and receptors [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Plasma Tsukushi Concentration Is Associated with High Levels of Insulin and FGF21 and Low Level of Total Cholesterol in a General Population without Medication

et al. 2022

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Tsukushi (TSK) is a member of the small leucine-rich proteoglycan family that controls developmental processes and organogenesis. TSK was also identified as a new hepatokine, which is mainly expressed in the liver, and is secreted by hepatocytes, to regulate energy and glycolipid metabolism in response to nonalcoholic fatty liver disease. However, the role of plasma TSK, especially its role in the general population, has not been fully addressed. We investigated the associations between plasma TSK concentration and several metabolic markers, including fibroblast growth factor 21 (FGF21), a hepatokine, and adiponectin, an adipokine, in 253 subjects (men/women: 114/139) with no medication in the Tanno–Sobetsu Study, which employed a population-based cohort. There was no significant sex difference in plasma TSK concentration, and the level was positively correlated with the fatty liver index (FLI) (r = 0.131, p = 0.038), levels of insulin (r = 0.295, p < 0.001) and levels of FGF21 (r = 0.290, p < 0.001), and was negatively correlated with the total cholesterol level (r = −0.124, p = 0.049). There was no significant correlation between the TSK level and body mass index, waist circumference, adiponectin, high-density lipoprotein cholesterol or total bile acids. The multivariable regression analysis showed that high levels of insulin and FGF21 and a low level of total cholesterol were independent determinants of plasma TSK concentration, after adjustment for age, sex and FLI. In conclusion, plasma TSK concentration is independently associated with high levels of insulin and FGF21, a hepatokine, and a low level of total cholesterol, but not with adiposity and adiponectin, in a general population of subjects who have not taken any medications.

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“…Several of these genes are expressed in the brain, which is consistent with them having a role in complex behavioral traits such as cue-responsivity. For example, Tsku is a member of the small leucine-rich proteoglycans (SLRPs) family (Deng et al, 2021) and has established functions in the CNS where it is crucial for commissure development (Ito et al, 2010) and has recently been characterized for roles in hippocampal neuronal development (Ahmad et al, 2020). Other genes such as ALG8 have been identified by human GWAS of depression in smokers (Heinzman et al, 2019).…”

Section: Genes With Coding Polymorphismsmentioning

confidence: 99%

Genomic Loci Influencing Cue-Reactivity in Heterogeneous Stock Rats

King,

Chitre,

Leal-Gutiérrez

et al. 2024

Preprint

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Addiction vulnerability is associated with the tendency to attribute incentive salience to reward predictive cues; both addiction and the attribution of incentive salience are influenced by environmental and genetic factors. To characterize the genetic contributions to incentive salience attribution, we performed a genome-wide association study (GWAS) in a cohort of 1,645 genetically diverse heterogeneous stock (HS) rats. We tested HS rats in a Pavlovian conditioned approach task, in which we characterized the individual responses to food-associated stimuli (cues). Rats exhibited either cue-directed sign-tracking behavior or food-cup directed goal-tracking behavior. We then used the conditioned reinforcement procedure to determine whether rats would perform a novel operant response for unrewarded presentations of the cue. We found that these measures were moderately heritable (SNP heritability, h2 = .189-.215). GWAS identified 14 quantitative trait loci (QTLs) for 11 of the 12 traits we examined. Interval sizes of these QTLs varied widely. 7 traits shared a QTL on chromosome 1 that contained a few genes (e.g. Tenm4, Mir708) that have been associated with substance use disorders and other mental health traits in humans. Other candidate genes (e.g. Wnt11, Pak1) in this region had coding variants and expression-QTLs in mesocorticolimbic regions of the brain. We also conducted a Phenome-Wide Association Study (PheWAS) on other behavioral measures in HS rats and found that regions containing QTLs on chromosome 1 were also associated with nicotine self-administration in a separate cohort of HS rats. These results provide a starting point for the molecular genetic dissection of incentive salience and provide further support for a relationship between attribution of incentive salience and drug abuse-related traits.

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Novel roles of Tsukushi in signaling pathways and multiple disease processes

Cited by 9 publications

References 51 publications

Isolation of Reporter Cells That Respond to Vitamin A and/or D Using a piggyBac Transposon Promoter-Trapping Vector System

Isolation of Reporter Cells That Respond to Vitamin A and/or D Using a piggyBac Transposon Promoter-Trapping Vector System

Plasma Tsukushi Concentration Is Associated with High Levels of Insulin and FGF21 and Low Level of Total Cholesterol in a General Population without Medication

Genomic Loci Influencing Cue-Reactivity in Heterogeneous Stock Rats

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