Solute carrier nutrient transporters in rheumatoid arthritis fibroblast-like synoviocytes

Torres, Alyssa; Pedersen, Brian; Gumá, Mónica

doi:10.3389/fimmu.2022.984408

Cited by 8 publications

(7 citation statements)

References 82 publications

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“…Meta-analysis and genome-wide association study by Ben Hamda C. et al 16 showed SLC7A5 as one of the top shared upregulated DEGs in the meta-analysis that is from the same solute carrier family as solute carrier family 4 member 1 (SLC4A1) and as our top DEG SLC44A5 downregulated and overlapping in SCD non-treated over HC and SCD treated over HC. The solute carrier transporter families are known as metabolic "gatekeepers" of the cells with an important role in adaptive and innate immunity 39 . SLC4A1 also encodes Band 3 an important mebrane transporter protein in red cells, highlighting its role in membrane stability and anione transport in erythropoietic cells 15 , Human SLC4A1/AE1 mutations are known to cause human spherocytosis and stomatocytosis.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic gene profiles in anex vivomodel of erythropoiesis to unravel molecular pathomechanisms of Sickle Cell Disease

Tinguely,

Opitz,

Schaer

et al. 2023

Preprint

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Sickle cell disease (SCD) is an autosomal recessive, single gene disorder caused by a point mutation in the beta globin(HBB)gene. The single amino acid substitution of the haemoglobin molecule leads to aberrant β-chain formation, polymerizing sickled haemoglobin (HbS) molecules together during episodes of deoxygenation and therefore causing intracellular sickling. Hydroxyurea (HU) is still the most indicated drug inducing fetal hemoglobin (HbF) production for SCD treatment, especially for the SCD patients with a severe clinical profile. In this study we could identify transcriptional profiles in erythroid cells of SCD patients, which have been treated with HU in comparison to untreated SCD patients and healthy controls.Our present transcriptomic profile analysis contained a new subset of genes identified for the first time as associated with SCD. In SCD non-treated-derived erythroid cells compared to controls, 398 differentially expressed genes (DEGs) were identified, of which 100 genes were upregulated and 298 genes were downregulated in the SCD patient cells. 65 DEGs were identified in SCD HU-treated patient-derived erythroid cells compared to controls, of which 37 genes were upregulated and 28 genes were downregulated. 212 DEGs were identified in SCD HU-treated patient-derived compared to SCD non-treated derived erythroid cells, of which 113 genes were upregulated and 99 genes were downregulated. 141 DEGs were identified in SCD derived erythroid cells compared to controls, of which 58 genes were upregulated and 83 genes were downregulated. We found biological processes such as oxidative phosphorylation pathway, Fanconi anaemia pathway, adaptive immune response or inflammatory response to be part of our significantly enriched Gene Ontology (GO) terms. Further genes encoding significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for proteasome, autophagy, immune response, platelet activation, as well as for natural killer cell (NK) cytotoxicity, oxidative phosphorylation, Fanconi anaemia pathway, ribosome biogenesis were upregulated in both SCD non treated and SCD HU-treated patient-derived erythroid cells in comparison to healthy controls. Our findings collectively suggest different as well as common molecular signatures between SCD non-treated, SCD HU-treated compared to HC. We could validate 12 of our top significant genes by qRT-PCR (calneuron 1 (CALN1), nucleoporin 85 (NUP85), tumor protein 63 (TP63), ras and rab interactor 2 (RIN2), solute carrier family 44 member 5 (SLC44A5), phenylethanolamine N-methyltransferase (PNMT), stabilin 1/ clever-1 (STAB1), SLX1 Homolog A, Structure-Specific Endonuclease Subunit (SLX1A), ATPase phospholipid transporting 9A (ATP9A), MSH5-SAPCD1, G protein subunit gamma 4 (GNG4) and glutathione S-transferase theta 2B (GSTT2B)) and compare their mRNA levels in bone marrow and spleen tissue from the Berkely SCD mouse model.In short, our study could identify new genes and pathways that may be involved in the SCD disease pathogenesis and that may be influenced by the HU treatment. The findings encourage future characterization of their roles in SCD to establish these findings as basis for new therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Transcriptomic gene profiles in anex vivomodel of erythropoiesis to unravel molecular pathomechanisms of Sickle Cell Disease

Tinguely,

Opitz,

Schaer

et al. 2023

Preprint

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“…Energy metabolism plays a crucial role in the stress adaptation and tolerance response of organisms, as extra energy is required to recover from and maintain the internal balance [ 80 ]. As the transporter proteins, the SLC family plays a significant role in maintaining the cellular metabolism and energy supply [ 81 , 82 , 83 ]. The identified genes ( Slc16a2 , Slc16a9 , Slc16a12 , Slc16a14 ) in our research belong to the Slc16a family, which is a group of transmembrane transport proteins mainly involved in the transport of organic acids such as lactate and pyruvate [ 81 , 84 ].…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Analysis of Heat Tolerance in F2 Progeny from the Hybridization between Two Congeneric Oyster Species

Du,

Jiang,

Wang

et al. 2023

IJMS

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As the world’s largest farmed marine animal, oysters have enormous economic and ecological value. However, mass summer mortality caused by high temperature poses a significant threat to the oyster industry. To investigate the molecular mechanisms underlying heat adaptation and improve the heat tolerance ability in the oyster, we conducted genome-wide association analysis (GWAS) analysis on the F2 generation derived from the hybridization of relatively heat-tolerant Crassostrea angulata ♀ and heat-sensitive Crassostrea gigas ♂, which are the dominant cultured species in southern and northern China, respectively. Acute heat stress experiment (semi-lethal temperature 42 °C) demonstrated that the F2 population showed differentiation in heat tolerance, leading to extremely differentiated individuals (approximately 20% of individuals die within the first four days with 10% survival after 14 days). Genome resequencing and GWAS of the two divergent groups had identified 18 significant SNPs associated with heat tolerance, with 26 candidate genes located near these SNPs. Eleven candidate genes that may associate with the thermal resistance were identified, which were classified into five categories: temperature sensor (Trpm2), transcriptional factor (Gata3), protein ubiquitination (Ube2h, Usp50, Uchl3), heat shock subfamily (Dnajc17, Dnaja1), and transporters (Slc16a9, Slc16a14, Slc16a9, Slc16a2). The expressional differentiation of the above genes between C. gigas and C. angulata under sublethal temperature (37 °C) further supports their crucial role in coping with high temperature. Our results will contribute to understanding the molecular mechanisms underlying heat tolerance, and provide genetic markers for heat-resistance breeding in the oyster industry.

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“…These activities promote the activation of FLS in multiple ways, whereas the use of related metabolic process inhibitors can reduce FLS migration, reducing bone erosion and joint edema. Moreover, they can be used as innovative targets for treating RA by targeting and regulating the activation of SLC family members during the development of new drugs ( 66 ).…”

Section: Altered Fls Metabolism and Intracellular Signaling Pathway T...mentioning

confidence: 99%

Metabolic changes in fibroblast-like synoviocytes in rheumatoid arthritis: state of the art review

Hu,

Li,

Zhang

et al. 2024

Front. Immunol.

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Fibroblast-like synoviocytes (FLS) are important components of the synovial membrane. They can contribute to joint damage through crosstalk with inflammatory cells and direct actions on tissue damage pathways in rheumatoid arthritis (RA). Recent evidence suggests that, compared with FLS in normal synovial tissue, FLS in RA synovial tissue exhibits significant differences in metabolism. Recent metabolomic studies have demonstrated that metabolic changes, including those in glucose, lipid, and amino acid metabolism, exist before synovitis onset. These changes may be a result of increased biosynthesis and energy requirements during the early phases of the disease. Activated T cells and some cytokines contribute to the conversion of FLS into cells with metabolic abnormalities and pro-inflammatory phenotypes. This conversion may be one of the potential mechanisms behind altered FLS metabolism. Targeting metabolism can inhibit FLS proliferation, providing relief to patients with RA. In this review, we aimed to summarize the evidence of metabolic changes in FLS in RA, analyze the mechanisms of these metabolic alterations, and assess their effect on RA phenotype. Finally, we aimed to summarize the advances and challenges faced in targeting FLS metabolism as a promising therapeutic strategy for RA in the future.

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Solute carrier nutrient transporters in rheumatoid arthritis fibroblast-like synoviocytes

Cited by 8 publications

References 82 publications

Transcriptomic gene profiles in anex vivomodel of erythropoiesis to unravel molecular pathomechanisms of Sickle Cell Disease

Transcriptomic gene profiles in anex vivomodel of erythropoiesis to unravel molecular pathomechanisms of Sickle Cell Disease

Genome-Wide Association Analysis of Heat Tolerance in F2 Progeny from the Hybridization between Two Congeneric Oyster Species

Metabolic changes in fibroblast-like synoviocytes in rheumatoid arthritis: state of the art review

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