Biology subjects

Terasmaa, A.

Publications and source records attributed to Terasmaa, A..

3 recordsLinked to original sources

bioRxiv2024

Endometriotic lesions exhibit distinct metabolic signature compared to paired eutopic endometrium at the single-cell level

Current therapeutics of endometriosis are limited to hormonal action on endometriotic lesions to disrupt their growth. Based on the recent findings of the high utilization of glycolysis over oxidative metabolism (Warburg-like effect) in endometriotic lesions, a new strategy of nonhormonal management by addressing cellular metabolism has been proposed. However, it remains unclear which cell types are metabolically altered and contribute to endometriotic lesion growth for targeting them with metabolic drugs. Using single-cell RNA-sequencing, we investigated the activity of twelve metabolic pathways and genes involved in steroidogenesis in paired samples of eutopic endometrium (EuE) and peritoneal lesions (ectopic endometrium, EcE) from women with confirmed endometriosis. We detected nine major cell clusters in both EuE and EcE. The metabolic pathways were differentially regulated in perivascular, stromal and to a lesser extent in endothelial cell clusters, with the highest changes in AMP-activated protein kinase signaling, Hypoxia-Inducible Factor-1 signaling, glutathione metabolism, oxidative phosphorylation, and glycolysis/gluconeogenesis. We identified a transcriptomic co-activation of glycolysis and oxidative metabolism in perivascular and stromal cells of EcE compared with EuE, suggesting that metabolic reprogramming may play a critical role in maintaining cell growth and survival of endometriotic lesions. Additionally, progesterone receptor was significantly downregulated in perivascular and endothelial cells of EcE. The expression of estrogen receptor 1 was significantly reduced in perivascular, stromal and endothelial cells of EcE. In parallel, perivascular cells exhibited a high expression of estrogen receptor 2 and HSD17B8 gene that encodes for protein converting estrone (E1) to estradiol (E2), while in endothelial cells HSD17B2 gene coding for enzyme converting E2 to E1 was downregulated. Overall, our results identified different expression patterns of energy metabolic pathways and steroidogenesis-related genes in perivascular, stromal, and endothelial cells in EcE compared with EuE. Perivascular cells, known to contribute to the restoration of endometrial stroma and angiogenesis, can be a potential target for non-hormonal treatment of endometriosis.

molecular biology↗

bioRxiv2020

Treatment with valproate downregulates the Agtr2 mRNA in rat lungs

GLP1 receptor agonist liraglutide has been shown to upregulate ACE2 expressions in several animal studies and thereby mediate strong positive stress response1. On the other hand, two in silico studies suggest that valproate downregulates ACE2 and AGTR2 gene expressions2,3. In this study, we have evaluated how these two widely used drugs, liraglutide and valproate, change the expression pattern of RAS system genes in the rat lungs. Our results indicate that eight-day treatment with valproate significantly downregulates the gene expression of Agtr2, Mas1 and Agrt1b in the rat lungs. These effects are reversed by co-administration of liraglutide.

molecular biology↗

bioRxiv2018

Soft drinks and monogenetic diabetes: a study on the Wolfram syndrome 1 (Wfs1) deficient mouse model

In a modern society, the risk of developing type II diabetes and obesity may be linked to the increased consumption of carbohydrate-rich drinks. Several genes, including Wolfram Syndrome 1 (WFS1), have been reported to increase susceptibility for developing type II diabetes. In this study we aimed to investigate the effect of chronic consumption of carbohydrate-rich drinks on weight gain, overall consumption of liquids, glucose tolerance and liver metabolism in Wfs1-deficient mice. Wfs1-deficient and wild-type mice were divided into three groups that consumed regular Coca-Cola, 20% sucrose solution or water ad libitum as the only source of liquid. During the experiment, daily liquid consumption was determined. After 30 days, total weight gain of mice was calculated and glucose tolerance test was performed. The liver tissue was analysed by means of untargeted and targeted metabolomics using liquid chromatography-mass spectrometry. Weight gain was strongly affected by mouse genotype (p<0.001), their drink (p<0.001) and the interaction of both genotype and drink (p<0.001). Coca-Cola significantly increased liquid consumption in knock-out mice. There was an effect of the drink (p<0.001) and the interaction between the genotype and treatment (p=0.02) on blood glucose level while Coca-Cola and 20% sucrose solution exacerbated glucose intolerance in the knock-out mice. In untargeted metabolic profiling, the water consuming wild-type and heterozygous mice were found to be the most distinctive from the mice with all other genotype and drink combinations. Targeted analysis revealed interactions between the genotype and drink regarding to glycolysis and lipogenesis. In the wild-type animals, carbohydrate overload was alleviated by converting glucose to lipids. However, the same mechanism is not implemented in knock-out animals, as lipolysis and gluconeogenesis are upregulated by Wfs1 deficiency. In conclusion, our study demonstrates a significant interaction between the genotype and the drink when comparing wild-type and Wfs1 knock-out mice consuming soft drinks.

biochemistry↗