Interference of KLF9 relieved the development of gestational diabetes mellitus by upregulating DDAH2

Gestational diabetes mellitus (GDM) is a situation where glucose intolerance is found in pregnant women without a previous diagnosis of diabetes. The role of Kruppel-like factor 9 (KLF9) has not been investigated in GDM, which constituted the aim of our study. HTR8/SVneo cells were induced by high g...

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Autores principales:	Weixia Chen, Huiqin Wang, Jing Liu, Kaixia Li
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	klf9 gestational diabetes mellitus ddah2 inflammation Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/79fe558803a84e1dad5f93d21d591db4
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spelling	oai:doaj.org-article:79fe558803a84e1dad5f93d21d591db42021-11-26T11:19:50ZInterference of KLF9 relieved the development of gestational diabetes mellitus by upregulating DDAH22165-59792165-598710.1080/21655979.2021.2005929https://doaj.org/article/79fe558803a84e1dad5f93d21d591db42021-11-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.2005929https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Gestational diabetes mellitus (GDM) is a situation where glucose intolerance is found in pregnant women without a previous diagnosis of diabetes. The role of Kruppel-like factor 9 (KLF9) has not been investigated in GDM, which constituted the aim of our study. HTR8/SVneo cells were induced by high glucose (HG) and pregnant mice were treated with streptozocin (STZ) to establish GDM model in vitro and in vivo, respectively. The expression level of KLF9 was detected by real-time PCR, immunohistochemical staining and western blot. Cell viability, apoptosis, inflammation, and oxidative stress were investigated by cell counting kit-8 (CCK-8), TUNEL, enzyme-linked immunosorbent assay (ELISA) and oxidative stress detection kits, respectively. The interaction of KLF9 with dimethylarginine dimethylaminohydrolase 2 (DDAH2) was predicted by bioinformatic tools and confirmed by luciferase reporter assay and chromatin immunoprecipitation (ChIP). The expression of KLF9 was increased in the placental tissues of GDM patients and HG-induced HTR8/SVneo cells. Silencing of KLF9 increased cell viability, recued cell apoptosis, and suppressed inflammation and oxidative stress in HG-induced HTR8/SVneo cells. KLF9 could bind to DDAH2 promoter and negatively regulate DDAH2 expression. Inhibition of DDAH2 partly weakened the effects of KLF9 silencing on cell apoptosis, inflammation and oxidative stress. The suppressive effects of KLF9 silencing on blood glucose and insulin concentration in vivo were also abolished by DDAH2 knockdown. In conclusion, we provided evidence that interference of KLF9 could hinder the development of GDM by alleviating cell apoptosis, inflammation and oxidative stress through upregulating DDAH2, which might instruct the targeting therapies against GDM.Weixia ChenHuiqin WangJing LiuKaixia LiTaylor & Francis Grouparticleklf9gestational diabetes mellitusddah2inflammationBiotechnologyTP248.13-248.65ENBioengineered, Vol 0, Iss 0 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	klf9 gestational diabetes mellitus ddah2 inflammation Biotechnology TP248.13-248.65
spellingShingle	klf9 gestational diabetes mellitus ddah2 inflammation Biotechnology TP248.13-248.65 Weixia Chen Huiqin Wang Jing Liu Kaixia Li Interference of KLF9 relieved the development of gestational diabetes mellitus by upregulating DDAH2
description	Gestational diabetes mellitus (GDM) is a situation where glucose intolerance is found in pregnant women without a previous diagnosis of diabetes. The role of Kruppel-like factor 9 (KLF9) has not been investigated in GDM, which constituted the aim of our study. HTR8/SVneo cells were induced by high glucose (HG) and pregnant mice were treated with streptozocin (STZ) to establish GDM model in vitro and in vivo, respectively. The expression level of KLF9 was detected by real-time PCR, immunohistochemical staining and western blot. Cell viability, apoptosis, inflammation, and oxidative stress were investigated by cell counting kit-8 (CCK-8), TUNEL, enzyme-linked immunosorbent assay (ELISA) and oxidative stress detection kits, respectively. The interaction of KLF9 with dimethylarginine dimethylaminohydrolase 2 (DDAH2) was predicted by bioinformatic tools and confirmed by luciferase reporter assay and chromatin immunoprecipitation (ChIP). The expression of KLF9 was increased in the placental tissues of GDM patients and HG-induced HTR8/SVneo cells. Silencing of KLF9 increased cell viability, recued cell apoptosis, and suppressed inflammation and oxidative stress in HG-induced HTR8/SVneo cells. KLF9 could bind to DDAH2 promoter and negatively regulate DDAH2 expression. Inhibition of DDAH2 partly weakened the effects of KLF9 silencing on cell apoptosis, inflammation and oxidative stress. The suppressive effects of KLF9 silencing on blood glucose and insulin concentration in vivo were also abolished by DDAH2 knockdown. In conclusion, we provided evidence that interference of KLF9 could hinder the development of GDM by alleviating cell apoptosis, inflammation and oxidative stress through upregulating DDAH2, which might instruct the targeting therapies against GDM.
format	article
author	Weixia Chen Huiqin Wang Jing Liu Kaixia Li
author_facet	Weixia Chen Huiqin Wang Jing Liu Kaixia Li
author_sort	Weixia Chen
title	Interference of KLF9 relieved the development of gestational diabetes mellitus by upregulating DDAH2
title_short	Interference of KLF9 relieved the development of gestational diabetes mellitus by upregulating DDAH2
title_full	Interference of KLF9 relieved the development of gestational diabetes mellitus by upregulating DDAH2
title_fullStr	Interference of KLF9 relieved the development of gestational diabetes mellitus by upregulating DDAH2
title_full_unstemmed	Interference of KLF9 relieved the development of gestational diabetes mellitus by upregulating DDAH2
title_sort	interference of klf9 relieved the development of gestational diabetes mellitus by upregulating ddah2
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/79fe558803a84e1dad5f93d21d591db4
work_keys_str_mv	AT weixiachen interferenceofklf9relievedthedevelopmentofgestationaldiabetesmellitusbyupregulatingddah2 AT huiqinwang interferenceofklf9relievedthedevelopmentofgestationaldiabetesmellitusbyupregulatingddah2 AT jingliu interferenceofklf9relievedthedevelopmentofgestationaldiabetesmellitusbyupregulatingddah2 AT kaixiali interferenceofklf9relievedthedevelopmentofgestationaldiabetesmellitusbyupregulatingddah2
_version_	1718409480782217216

Interference of KLF9 relieved the development of gestational diabetes mellitus by upregulating DDAH2

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