PMID- 32994409 OWN - NLM STAT- MEDLINE DCOM- 20210113 LR - 20210929 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 10 IP - 1 DP - 2020 Sep 29 TI - Omidenepag, a non-prostanoid EP2 receptor agonist, induces enlargement of the 3D organoid of 3T3-L1 cells. PG - 16018 LID - 10.1038/s41598-020-72538-x [doi] LID - 16018 AB - 2D and 3D cultures of 3T3-L1 cells were employed in a study of the effects of Omidenepag (OMD), interacting with a non-prostanoid EP2 receptor, on adipogenesis. Upon adipogenesis, the effects on lipid staining, the mRNA expression of adipogenesis-related genes (Ppargamma, CEBPa, Ap2, and Glut4) and the extracellular matrix (ECM) including collagen type 1, 4 and 6, and fibronectin, and the size and physical property of 3D organoids were compared between groups that had been treated with EP2 agonists (butaprost and OMD) and PGF2alpha. Upon adipogenesis, these significantly suppressed lipid staining and the mRNA expression of related genes. EP2 agonists and PGF2alpha influenced the mRNA expression of ECM in different manners, and these effects were also different between 2 and 3D cultures. Examining the physical properties by a microsqueezer indicated that the solidity of the 3D organoids became significantly lowered upon adipogenesis and these effects were not affected by EP2 agonists. In contrast, 3D organoid stiffness was markedly enhanced by the presence of PGF2alpha. These observations indicate that EP2 agonists affect the adipogenesis of 3T3-L1 cells in different manners, as compared to PGF2alpha, suggesting that OMD may not induce PGF2alpha related orbital fat atrophy, called the deepening of the upper eyelid sulcus (DUES). FAU - Ida, Yosuke AU - Ida Y AD - Departments of Ophthalmology, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Hikage, Fumihito AU - Hikage F AD - Departments of Ophthalmology, Sapporo Medical University School of Medicine, Sapporo, Japan. fuhika@gmail.com. FAU - Umetsu, Araya AU - Umetsu A AD - Departments of Ophthalmology, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Ida, Haruka AU - Ida H AD - Departments of Ophthalmology, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Ohguro, Hiroshi AU - Ohguro H AD - Departments of Ophthalmology, Sapporo Medical University School of Medicine, Sapporo, Japan. LA - eng PT - Comparative Study PT - Journal Article DEP - 20200929 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Pyrazoles) RN - 0 (Pyridines) RN - B7IN85G1HY (Dinoprost) RN - G0G0H52U6K (omidenepag isopropyl) RN - TE7660XO1C (Glycine) SB - IM MH - 3T3-L1 Cells MH - Adipogenesis/*drug effects MH - Animals MH - Cell Culture Techniques MH - Dinoprost/*pharmacology MH - Extracellular Matrix/drug effects/genetics MH - Gene Expression Regulation/drug effects MH - Gene Regulatory Networks/drug effects MH - Glycine/*analogs & derivatives/pharmacology MH - Mice MH - Organ Size/drug effects MH - Organoids/chemistry/*cytology/drug effects MH - Pyrazoles/*pharmacology MH - Pyridines/*pharmacology PMC - PMC7524797 COIS- The authors declare no competing interests. EDAT- 2020/10/01 06:00 MHDA- 2021/01/14 06:00 PMCR- 2020/09/29 CRDT- 2020/09/30 06:07 PHST- 2020/06/30 00:00 [received] PHST- 2020/09/02 00:00 [accepted] PHST- 2020/09/30 06:07 [entrez] PHST- 2020/10/01 06:00 [pubmed] PHST- 2021/01/14 06:00 [medline] PHST- 2020/09/29 00:00 [pmc-release] AID - 10.1038/s41598-020-72538-x [pii] AID - 72538 [pii] AID - 10.1038/s41598-020-72538-x [doi] PST - epublish SO - Sci Rep. 2020 Sep 29;10(1):16018. doi: 10.1038/s41598-020-72538-x.