Influence of high glucose in the expression of miRNAs and IGF1R signaling pathway in human myometrial explants

Autor(es)

Favaro, Rodolfo R. ^{[1, 2]} ; Morales-Prieto, Diana M. ^[2] ; Herrmann, Joerg ^[3] ; Sonnemann, Juergen ^[4] ; Schleussner, Ekkehard ^[2] ; Markert, Udo R. ^[2] ; Zorn, Telma M. T. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, Lab Reprod & Extracellular Matrix Biol, Sao Paulo - Brazil

^[2] Jena Univ Hosp, Dept Obstet, Placenta Lab, Jena - Germany

^[3] Hufeland Klinikum, Dept Gynecol & Obstet, Weimar - Germany

^[4] Jena Univ Hosp, Dept Pediat Hematol & Oncol, Childrens Clin, Jena - Germany

• Tipo de documento: Artigo Científico
• Fonte: ARCHIVES OF GYNECOLOGY AND OBSTETRICS; v. 303, n. 6 FEB 2021.
• Citações Web of Science: 0

Resumo

Purpose Several roles are attributed to the myometrium including sperm and embryo transport, menstrual discharge, control of uterine blood flow, and labor. Although being a target of diabetes complications, the influence of high glucose on this compartment has been poorly investigated. Both miRNAs and IGF1R are associated with diabetic complications in different tissues. Herein, we examined the effects of high glucose on the expression of miRNAs and IGF1R signaling pathway in the human myometrium. Methods Human myometrial explants were cultivated for 48 h under either high or low glucose conditions. Thereafter, the conditioned medium was collected for biochemical analyses and the myometrial samples were processed for histological examination as well as miRNA and mRNA expression profiling by qPCR. Results Myometrial structure and morphology were well preserved after 48 h of cultivation in both high and low glucose conditions. Levels of lactate, creatinine, LDH and estrogen in the supernatant were similar between groups. An explorative screening by qPCR arrays revealed that 6 out of 754 investigated miRNAs were differentially expressed in the high glucose group. Data validation by single qPCR assays confirmed diminished expression of miR-215-5p and miR-296-5p, and also revealed reduced miR-497-3p levels. Accordingly, mRNA levels of IGF1R and its downstream mediators FOXO3 and PDCD4, which are potentially targeted by miR-497-3p, were elevated under high glucose conditions. In contrast, mRNA expression of IGF1, PTEN, and GLUT1 was unchanged. Conclusions The human myometrium responds to short-term exposure (48 h) to high glucose concentrations by regulating the expression of miRNAs, IGF1R and its downstream targets. (AU)

• Processo FAPESP: 14/23517-1 - O diabetes tipo 1 altera o perfil de expressão de microRNAs no útero de fêmeas de camundongos ovarectomizadas e submetidas ou não a reposição por estrógeno?
• Beneficiário: Rodolfo Favaro Ribeiro
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 13/16922-4 - Caracterização imunohistoquímica dos componentes da matriz extracelular durante o desenvolvimento do deciduoma e estudo do efeito dos hormônios ovarianos sob a expressão e síntese de moléculas da matriz extracelular por células deciduais in vitro
• Beneficiário: Telma Maria Tenório Zorn
• Modalidade de apoio: Auxílio à Pesquisa - Regular