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Petrovic, V.

Publications and source records attributed to Petrovic, V..

2 recordsLinked to original sources

EXPRESSION OF ANO1 IN HUMAN GASTROINTESTINAL TRACT DURING EMBRYONIC AND FETAL DEVELOPMENT

Anoctamin 1 (ANO1, TMEM16A) is a transmembrane protein belonging to the ANO family, with a role in the formation of calcium-activated chloride channels (CaCC). It is included in the regulation of physiological processes such as muscle contraction, gastrointestinal motility, secretion, and electrical excitability. Also, recent data suggest that ANO1 is a specific marker for interstitial cells of Cajal (ICC). The aim of the paper was to examine the spatial and temporal distribution of ANO1 in the stomach, small intestine, and large intestine during embryofetal development as a potential marker for the differentiation of ICC and smooth muscle cells. As a material, we used 2 human embryos and samples from 21 human fetuses. The tissue samples were routinely processed into paraffin blocks, and 5 {micro}m-thick sections were immunostained for ANO1. Our results show that ANO1 appears during embryonic development (8th week), and its expression continues through the fetal stages. Epithelial, endothelial and ICC cells consistently expressed ANO1 in all examined samples. Smooth muscle cells showed strong expression in muscularis propria, however by the 25th week this immunopositivity was absent from outer muscle layers in stomach and large intestine. In conclusion, ANO1 can be considered as a reliable marker for following the differentiation of SMC and ICC during embryonic and fetal development.

developmental biology↗

PCNA has specific functions in regulation of metabolism in haematological cells

PCNAs essential roles in DNA replication and repair are well established, while its recently discovered cytosolic roles are less explored. Here we show that impairing PCNAs cytosolic scaffold functions led to massive changes in cellular signaling, and most strikingly, a strong reduction in glycolytic metabolite and nucleoside phosphate pools in haematological cancer cells. This was not detected in cells from solid tissues nor in primary monocytes from healthy donors. However, lipopolysaccharide stimulated monocytes responded to targeting PCNAs scaffold function similarly to haematological cancer cells, suggesting that cellular stress is an important factor for the observed response. Integrated transcriptome, proteome and metabolome analysis revealed that pathways involved in protein stability/folding and immune responses were affected in haematopoietic cancer cells. Altogether, our data suggests that PCNA has an important role in regulation of cytoplasmic stress via regulation of central carbon metabolism in haematological cells, which potentially can be targeted in cancer treatment. HighlightA strong reduction in glycolytic metabolites and the nucleoside phosphate pools was detected in haematological cancer cells upon inhibiting PCNA scaffold functions. These metabolic changes were not found in cancer cells from other tissues, indicating a special role of PCNA in regulation of metabolism in cells of haematological origin.

cell biology↗