Cargando…

Ligustrazine inhibits inflammatory response of human endometrial stromal cells through the STAT3/IGF2BP1/RELA axis

CONTEXT: Endometriosis (EMs) is a gynecological disorder. Ligustrazine has been reported to exert an anti-inflammatory effect on EMs. However, the underlying mechanisms are not completely understood. OBJECTIVE: To investigate the effects of ligustrazine on the progression of EMs and the underlying r...

Descripción completa

Detalles Bibliográficos
Autores principales: Feng, Ying, Dong, Han, Zheng, Liyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10132247/
https://www.ncbi.nlm.nih.gov/pubmed/37095705
http://dx.doi.org/10.1080/13880209.2023.2195883
_version_ 1785031355068841984
author Feng, Ying
Dong, Han
Zheng, Liyan
author_facet Feng, Ying
Dong, Han
Zheng, Liyan
author_sort Feng, Ying
collection PubMed
description CONTEXT: Endometriosis (EMs) is a gynecological disorder. Ligustrazine has been reported to exert an anti-inflammatory effect on EMs. However, the underlying mechanisms are not completely understood. OBJECTIVE: To investigate the effects of ligustrazine on the progression of EMs and the underlying regulatory mechanisms. MATERIALS AND METHODS: Human endometrial stromal cells (HESCs) were isolated from patients with EMs or control subjects. HESCs were treated with 25, 50, 100, or 200 μM ligustrazine for 1, 3, 6, or 12 h. Western blot and enzyme-linked immunosorbent assays were performed to determine the levels of proteins and inflammatory cytokines, respectively. The binding between STAT3 and insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) was assessed by chromatin immunoprecipitation and dual-luciferase reporter assays. The relationship between IGF2BP1 and RELA was assessed by RNA immunoprecipitation and RNA pull-down assay. RESULTS: Phosphorylated STAT3, IGF2BP1, RELA, TNF-α, IL-6, and IL-1β were upregulated in EMs tissues compared with control tissues (by 1.79-, 2.55-, 1.58-, 3.01-, 2.55-, and 3.34-fold, respectively). Ligustrazine inhibited the expression of p-STAT3, IGF2BP1, RELA, IL-6, TNF-α, and IL-1β. Overexpression of STAT3 promoted RELA-mediated inflammatory responses, while ligustrazine (100 µM) notably reversed this phenomenon. Ligustrazine also alleviated RELA-induced inflammation via downregulating IGF2BP1. STAT3 bound to the promoter of IGF2BP1, and IGF2BP1 bound to the RELA mRNA. DISCUSSION AND CONCLUSION: Ligustrazine inhibited inflammation in EMs via regulating the STAT3/IGF2BP1/RELA axis. These findings propose a new agent against EMs and support the development of ligustrazine-based treatment strategies for EMs.
format Online
Article
Text
id pubmed-10132247
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Taylor & Francis
record_format MEDLINE/PubMed
spelling pubmed-101322472023-04-27 Ligustrazine inhibits inflammatory response of human endometrial stromal cells through the STAT3/IGF2BP1/RELA axis Feng, Ying Dong, Han Zheng, Liyan Pharm Biol Research Article CONTEXT: Endometriosis (EMs) is a gynecological disorder. Ligustrazine has been reported to exert an anti-inflammatory effect on EMs. However, the underlying mechanisms are not completely understood. OBJECTIVE: To investigate the effects of ligustrazine on the progression of EMs and the underlying regulatory mechanisms. MATERIALS AND METHODS: Human endometrial stromal cells (HESCs) were isolated from patients with EMs or control subjects. HESCs were treated with 25, 50, 100, or 200 μM ligustrazine for 1, 3, 6, or 12 h. Western blot and enzyme-linked immunosorbent assays were performed to determine the levels of proteins and inflammatory cytokines, respectively. The binding between STAT3 and insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) was assessed by chromatin immunoprecipitation and dual-luciferase reporter assays. The relationship between IGF2BP1 and RELA was assessed by RNA immunoprecipitation and RNA pull-down assay. RESULTS: Phosphorylated STAT3, IGF2BP1, RELA, TNF-α, IL-6, and IL-1β were upregulated in EMs tissues compared with control tissues (by 1.79-, 2.55-, 1.58-, 3.01-, 2.55-, and 3.34-fold, respectively). Ligustrazine inhibited the expression of p-STAT3, IGF2BP1, RELA, IL-6, TNF-α, and IL-1β. Overexpression of STAT3 promoted RELA-mediated inflammatory responses, while ligustrazine (100 µM) notably reversed this phenomenon. Ligustrazine also alleviated RELA-induced inflammation via downregulating IGF2BP1. STAT3 bound to the promoter of IGF2BP1, and IGF2BP1 bound to the RELA mRNA. DISCUSSION AND CONCLUSION: Ligustrazine inhibited inflammation in EMs via regulating the STAT3/IGF2BP1/RELA axis. These findings propose a new agent against EMs and support the development of ligustrazine-based treatment strategies for EMs. Taylor & Francis 2023-04-24 /pmc/articles/PMC10132247/ /pubmed/37095705 http://dx.doi.org/10.1080/13880209.2023.2195883 Text en © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
spellingShingle Research Article
Feng, Ying
Dong, Han
Zheng, Liyan
Ligustrazine inhibits inflammatory response of human endometrial stromal cells through the STAT3/IGF2BP1/RELA axis
title Ligustrazine inhibits inflammatory response of human endometrial stromal cells through the STAT3/IGF2BP1/RELA axis
title_full Ligustrazine inhibits inflammatory response of human endometrial stromal cells through the STAT3/IGF2BP1/RELA axis
title_fullStr Ligustrazine inhibits inflammatory response of human endometrial stromal cells through the STAT3/IGF2BP1/RELA axis
title_full_unstemmed Ligustrazine inhibits inflammatory response of human endometrial stromal cells through the STAT3/IGF2BP1/RELA axis
title_short Ligustrazine inhibits inflammatory response of human endometrial stromal cells through the STAT3/IGF2BP1/RELA axis
title_sort ligustrazine inhibits inflammatory response of human endometrial stromal cells through the stat3/igf2bp1/rela axis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10132247/
https://www.ncbi.nlm.nih.gov/pubmed/37095705
http://dx.doi.org/10.1080/13880209.2023.2195883
work_keys_str_mv AT fengying ligustrazineinhibitsinflammatoryresponseofhumanendometrialstromalcellsthroughthestat3igf2bp1relaaxis
AT donghan ligustrazineinhibitsinflammatoryresponseofhumanendometrialstromalcellsthroughthestat3igf2bp1relaaxis
AT zhengliyan ligustrazineinhibitsinflammatoryresponseofhumanendometrialstromalcellsthroughthestat3igf2bp1relaaxis