Epithelial to mesenchymal transition in mammary gland tissue fibrosis and insights into drug therapeutics.

Autor:	Syed MA; Division of Animal Biotechnology, Faculty of Veterinary Sciences, Sher-e-Kashmir University of Agricultural Sciences and Technology of Kashmir, India, Srinagar, India., Bhat B; Division of Animal Biotechnology, Faculty of Veterinary Sciences, Sher-e-Kashmir University of Agricultural Sciences and Technology of Kashmir, India, Srinagar, India., Wali A; Department of Clinical Biochemistry, University of Kashmir, Srinagar, Jammu and Kashmir, India., Saleem A; Division of Animal Biotechnology, Faculty of Veterinary Sciences, Sher-e-Kashmir University of Agricultural Sciences and Technology of Kashmir, India, Srinagar, India., Ahmad Dar L; Division of Animal Biotechnology, Faculty of Veterinary Sciences, Sher-e-Kashmir University of Agricultural Sciences and Technology of Kashmir, India, Srinagar, India., Gugjoo MB; Division of Veterinary Surgery, Sher-e-Kashmir University of Agricultural Sciences and Technology of Kashmir, Faculty of Veterinary Sciences and Animal Husbandry, Shuhama, SKUAST-K, India, Srinagar, Jammu and Kashmir, India., Bhat S; Division of Animal Biotechnology, Faculty of Veterinary Sciences, Sher-e-Kashmir University of Agricultural Sciences and Technology of Kashmir, India, Srinagar, India., Saleem Bhat S; Division of Animal Biotechnology, Faculty of Veterinary Sciences, Sher-e-Kashmir University of Agricultural Sciences and Technology of Kashmir, India, Srinagar, India.
Jazyk:	angličtina
Zdroj:	PeerJ [PeerJ] 2023 May 09; Vol. 11, pp. e15207. Date of Electronic Publication: 2023 May 09 (Print Publication: 2023).
DOI:	10.7717/peerj.15207
Abstrakt:	Background: The epithelial-mesenchymal transition (EMT) is a multi-step morphogenetic process in which epithelial cells lose their epithelial properties and gain mesenchymal characteristics. The process of EMT has been shown to mediate mammary gland fibrosis. Understanding how mesenchymal cells emerge from an epithelial default state will aid in unravelling the mechanisms that control fibrosis and, ultimately, in identifying therapeutic targets to alleviate fibrosis. Methods: The effects of EGF and high glucose (HG) on EMT in mammary epithelial cells, MCF10A and GMECs, as well as their pathogenic role, were studied. In-silico analysis was used to find interacting partners and protein-chemical/drug molecule interactions. Results: On treatment with EGF and/or HG, qPCR analysis showed a significant increase in the gene expression of EMT markers and downstream signalling genes. The expression of these genes was reduced on treatment with EGF+HG combination in both cell lines. The protein expression of COL1A1 increased as compared to the control in cells treated with EGF or HG alone, but when the cells were treated with EGF and HG together, the protein expression of COL1A1 decreased. ROS levels and cell death increased in cells treated with EGF and HG alone, whereas cells treated with EGF and HG together showed a decrease in ROS production and apoptosis. In-silico analysis of protein-protein interactions suggest the possible role of MAPK1, actin alpha 2 (ACTA2), COL1A1, and NF κ B1 in regulating TGF β 1, ubiquitin C (UBC), specificity protein 1 (SP1) and E1A binding protein P300 (EP300). Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment suggests advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signalling pathway, relaxin signalling pathway and extra cellular matrix (ECM) receptor interactions underlying fibrosis mechanism. Conclusion: This study demonstrates that EGF and HG induce EMT in mammary epithelial cells and may also have a role in fibrosis. Competing Interests: Mudasir Ahmad Syed is an Academic Editor for PeerJ. (©2023 Syed et al.)
Databáze:	MEDLINE
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