Prostaglandin F2\u03b1 agonist-induced suppression of 3T3-L1 cell adipogenesis affects spatial formation of extra-cellular matrix

Yosuke Ida,Hiroshi Ohguro,Fumihito Hikage,Kaku Itoh,Haruka Ida

doi:10.1038/s41598-020-64674-1

Yosuke Ida, Hiroshi Ohguro + Show 3 more

Open Access

https://doi.org/10.1038/s41598-020-64674-1

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Journal: Scientific Reports	Publication Date: May 14, 2020
Citations: 50	License type: open-access

Affiliation: Sapporo Medical University

Abstract

To establish a deepening of the upper eyelid sulcus (DUES) model that can be induced by prostaglandin (PG) analogues, a three-dimension (3D) tissue culture was employed. Upon adipogenesis of the 3T3-L1 organoid, the effects of either Bimatoprost acid (BIM-A), or PGF2α were examined. During the adipogenesis, organoid size, lipid staining by BODIPY and expression of the extracellular matrix (ECM) by immunocytochemistry and/or quantitative PCR were employed. The size of the organoid increased remarkably during the adipogenesis, while such increases were significantly inhibited by the presence of PGF2α or BIM-A. BODIPY positive lipid-laden cells significantly increased during the adipogenesis, while in contrast they were greatly suppressed by the presence of PGF2α. Characteristic and spatial changes in ECM expressions observed upon adipogenesis were greatly modified by the presence of PGs. Our present study using a 3D tissue culture may be a suitable strategy toward understanding disease etiology of DUES.

Highlights

To establish a deepening of the upper eyelid sulcus (DUES) model that can be induced by prostaglandin (PG) analogues, a three-dimension (3D) tissue culture was employed
During the course of the 3D culture, premature organoids grew into their matured form with a number of lipids marked by arrows (Fig. 1A, lower panel)
Other drugs like timolol and benzalkonium chloride didn’t show significant suppression and cytotoxic effects toward adipocytes. Such effects of Prostaglandin analogues (PGs) toward adipocytes were thought to be involved in the etiology of DUES

Summary

Introduction

To establish a deepening of the upper eyelid sulcus (DUES) model that can be induced by prostaglandin (PG) analogues, a three-dimension (3D) tissue culture was employed. To reach PPARγ induced maturity of the adipocyte differentiation there are known to be modulated by some stimulators including PGs, insulin-like growth factor 1 (IGF-1), insulin, cAMP, triiodothyronine, macrophage colony stimulating factor, fatty acids, and glucocorticoids[16,17], as well as inhibitors including glycoproteins, transforming growth factor-β (TGF-β), inflammatory cytokines and growth hormone[18]. Among these factors, PGs is well known to be one of the factors that affect the adipogenesis, since. Adipogenesis of 3T3-L1 (preadipocyte cell line) is significantly inhibited by treatment with PGs including PGF2α or fluprostenol, a prostanoid FP2 receptor agonist[20]

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Results

Conclusion