Inflammation‐associated upregulation of the sulfated steroid transporter Slc10a6 in mouse liver and macrophage cell lines

Kosters, Astrid; Abebe, Demesew F.; Felix, Julio C.; Dawson, Paul A.; Karpen, Saul J.

doi:10.1111/hepr.12609

Cited by 6 publications

(7 citation statements)

References 44 publications

(94 reference statements)

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“…We identified several genes, which determine cholesterol flux, as upregulated in liver ECs of GF mice relative to their CONV-R counterparts ( Figure 2 C). In contrast to a previous study showing the regulation of the Na + -dependent bile acid transporter solute carrier family 10 member 6 ( Slc10a6 ) via lipopolysaccharide signaling, depending on the nuclear receptor farnesoid X receptor (FXR) and the retinoid X receptor ( Kosters et al., 2016 ; Sawkat Anwer and Stieger, 2014 ), we found increased expression of Slc10a6 at GF housing conditions. In line with increased plasma lipoprotein levels at chow diet at GF housing conditions ( Kiouptsi et al., 2019 ), expression of Tsc22d1 , encoding a transcription factor that is critically involved in the formation of high-density lipoprotein (HDL) particles ( Jäger et al., 2014 ), was increased in the hepatic endothelium of GF mice.…”

Section: Resultscontrasting

confidence: 99%

The gut microbiota instructs the hepatic endothelial cell transcriptome

et al. 2021

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Summary The gut microbiota affects remote organ functions but its impact on organotypic endothelial cell (EC) transcriptomes remains unexplored. The liver endothelium encounters microbiota-derived signals and metabolites via the portal circulation. To pinpoint how gut commensals affect the hepatic sinusoidal endothelium, a magnetic cell sorting protocol, combined with fluorescence-activated cell sorting, was used to isolate hepatic sinusoidal ECs from germ-free (GF) and conventionally raised (CONV-R) mice for transcriptome analysis by RNA sequencing. This resulted in a comprehensive map of microbiota-regulated hepatic EC-specific transcriptome profiles. Gene Ontology analysis revealed that several functional processes in the hepatic endothelium were affected. The absence of microbiota influenced the expression of genes involved in cholesterol flux and angiogenesis. Specifically, genes functioning in hepatic endothelial sphingosine metabolism and the sphingosine-1-phosphate pathway showed drastically increased expression in the GF state. Our analyses reveal a prominent role for the microbiota in shaping the transcriptional landscape of the hepatic endothelium.

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Section: Resultscontrasting

confidence: 99%

The gut microbiota instructs the hepatic endothelial cell transcriptome

et al. 2021

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“…A previous study showed that Slc10a6 mRNA levels were significantly induced by LPS in the mouse liver and WAT ( Kosters et al, 2016 ). To further investigate the response of peripheral intracrine tissues to inflammation, gene expression analysis of steroid sulfate carriers was performed in LPS-induced 3T3-L1 adipocytes and mouse adipose tissues.…”

Section: Resultsmentioning

confidence: 99%

“…A global gene expression analysis in mice demonstrated that Soat is among the most strongly induced genes by LPS in the liver and macrophages ( Kosters et al, 2016 ). In addition, Slc10a6 mRNA expression was upregulated in the liver of mice treated with the cytokine IL-1β.…”

Section: Discussionmentioning

confidence: 99%

“…However, Soat shows higher expression in the BAT and is less expressed in WAT of untreated mice when compared to that in the testes. In contrast, Slc10a6 mRNA levels are upregulated in WAT and downregulated in BAT specimens of LPS-induced mice ( Kosters et al, 2016 ). We found that LPS-elicited inflammation induced a significant increase in Slc10a6 mRNA expression in WAT, SAT, and PAT specimens of mice in vivo and in mature 3T3-L1 adipocytes in vitro ( Figure 4 ).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, by immunohistochemistry, Soat protein was localized in bronchial epithelial cells of the lung, in primary and secondary spermatocytes, in the round spermatids within the seminiferous tubules of the testis, in the epidermis of the skin, and in the urinary epithelium of the bladder ( Grosser et al, 2013 ). In a recent study, Slc10a6 mRNA was among the most strongly induced transcripts in mice exposed to lipopolysaccharide (LPS), suggesting that Slc10a6 represents an inflammation-responsive gene ( Kosters et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

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Role of the Steroid Sulfate Uptake Transporter Soat (Slc10a6) in Adipose Tissue and 3T3-L1 Adipocytes

Karakuş

Schmid

Leiting

et al. 2022

Front. Mol. Biosci.

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In addition to the endocrine and paracrine systems, peripheral tissues such as gonads, skin, and adipose tissue are involved in the intracrine mechanisms responsible for the formation of sex steroids via the transformation of dehydroepiandrosterone and dehydroepiandrosterone sulfate (DHEA/DHEAS) into potent androgenic and estrogenic hormones. Numerous studies have examined the relationship between overweight, central obesity, and plasma levels of DHEA and DHEAS. The sodium-dependent organic anion transporter Soat (Slc10a6) is a plasma membrane uptake transporter for sulfated steroids. Significantly increased expression of Slc10a6 mRNA has been previously described in organs and tissues of lipopolysaccharide (LPS)-treated mice, including white adipose tissue. These findings suggest that Soat plays a role in the supply of steroids in peripheral target tissues. The present study aimed to investigate the expression of Soat in adipocytes and its role in adipogenesis. Soat expression was analyzed in mouse white intra-abdominal (WAT), subcutaneous (SAT), and brown (BAT) adipose tissue samples and in murine 3T3-L1 adipocytes. In addition, adipose tissue mass and size of the adipocytes were analyzed in wild-type and Slc10a6−/− knockout mice. Soat expression was detected in mouse WAT, SAT, and BAT using immunofluorescence. The expression of Slc10a6 mRNA was significantly higher in 3T3-L1 adipocytes than that of preadipocytes and was significantly upregulated by exposure to lipopolysaccharide (LPS). Slc10a6 mRNA levels were also upregulated in the adipose tissue of LPS-treated mice. In Slc10a6−/− knockout mice, adipocytes increased in size in the WAT and SAT of female mice and in the BAT of male mice, suggesting adipocyte hypertrophy. The serum levels of adiponectin, resistin, and leptin were comparable in wild-type and Slc10a6−/− knockout mice. The treatment of 3T3-L1 adipocytes with DHEA significantly reduced lipid accumulation, while DHEAS did not have a significant effect. However, following LPS-induced Soat upregulation, DHEAS also significantly inhibited lipid accumulation in adipocytes. In conclusion, Soat-mediated import of DHEAS and other sulfated steroids could contribute to the complex pathways of sex steroid intracrinology in adipose tissues. Although in cell cultures the Soat-mediated uptake of DHEAS appears to reduce lipid accumulation, in Slc10a6−/− knockout mice, the Soat deletion induced adipocyte hyperplasia through hitherto unknown mechanisms.

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SLC10A7, an orphan member of the SLC10 family involved in congenital disorders of glycosylation

et al. 2022

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SLC10A7, encoded by the so-called SLC10A7 gene, is the seventh member of a human sodium/bile acid cotransporter family, known as the SLC10 family. Despite similarities with the other members of the SLC10 family, SLC10A7 does not exhibit any transport activity for the typical SLC10 substrates and is then considered yet as an orphan carrier. Recently, SLC10A7 mutations have been identified as responsible for a new Congenital Disorder of Glycosylation (CDG). CDG are a family of rare and inherited metabolic disorders where glycosylation abnormalities lead to multisystemic defects. SLC10A7-CDG patients presented skeletal dysplasia with multiple large joints dislocations, short stature and amelogenesis imperfecta likely mediated by glycosaminoglycan (GAG) defects. Although it has been demonstrated that the transporter and substrate specificities of SLC10A7, if any, differ from those of the main members of the protein family, SLC10A7 seems to play a role in Ca 2+ regulation and is involved in proper glycosaminoglycan biosynthesis, especially heparan-sulfate, and N-glycosylation. This paper will review our current knowledge on the known and predicted structural and functional properties of this fascinating protein, and its link with the glycosylation process.

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Inflammation‐associated upregulation of the sulfated steroid transporter Slc10a6 in mouse liver and macrophage cell lines

Cited by 6 publications

References 44 publications

The gut microbiota instructs the hepatic endothelial cell transcriptome

The gut microbiota instructs the hepatic endothelial cell transcriptome

Role of the Steroid Sulfate Uptake Transporter Soat (Slc10a6) in Adipose Tissue and 3T3-L1 Adipocytes

SLC10A7, an orphan member of the SLC10 family involved in congenital disorders of glycosylation

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