Effects of constitutively active IKKβ on cardiac development

Sachiko Sugioka; Shinya Ikeda; Masayuki Harada; Masako Kishihata; Isehaq Al-Huseini; Takeshi Kimura; Noboru Ashida

doi:10.1016/j.bbrc.2022.05.019

Effects of constitutively active IKKβ on cardiac development

Biochem Biophys Res Commun. 2022 Jul 23:614:169-174. doi: 10.1016/j.bbrc.2022.05.019. Epub 2022 May 10.

Authors

Sachiko Sugioka¹, Shinya Ikeda¹, Masayuki Harada¹, Masako Kishihata¹, Isehaq Al-Huseini¹, Takeshi Kimura¹, Noboru Ashida²

Affiliations

¹ Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan.
² Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan. Electronic address: nashida@kuhp.kyoto-u.ac.jp.

PMID: 35597154
DOI: 10.1016/j.bbrc.2022.05.019

Abstract

NF-κB is a major transcription factor regulating cell survival, organ development and inflammation, but its role in cardiac development has been inadequately explored. To examine this function, we generated mice in which IKKβ, an essential kinase for NF-κB activation, was constitutively activated in embryonic cardiomyocytes. For this purpose, we used smooth muscle-22α (SM22α)-Cre mice, which are frequently used for gene recombination in embryonic cardiomyocytes. Embryonic hearts of SM22αCre-CA (constitutively active) IKKβ^flox/flox mice revealed remarkably thin, spongy and hypoplastic myocardium. In exploring the mechanism, we found that the expression of bone morphogenetic protein 10 (BMP10) and T-box transcription factor 20 (Tbx20), major regulators of cardiac development, was significantly downregulated and upregulated, respectively, in the SM22αCre-CAIKKβ^flox/flox mice. We also generated NK2 homeobox 5 (Nkx2.5) Cre-CAIKKβ^flox/wt mice since Nkx2.5 is also expressed in embryonic cardiomyocytes and confirmed that the changes in these genes were also observed. These results implicated that the activation of NF-κB affects cardiac development.

Keywords: BMP10; Cardiac development; IKKβ; Noncompaction.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bone Morphogenetic Proteins / metabolism
Heart* / embryology
I-kappa B Kinase* / genetics
I-kappa B Kinase* / metabolism
Mice
Myocardium / metabolism
NF-kappa B* / metabolism
T-Box Domain Proteins / metabolism
Transcription Factors / metabolism

Substances

Bone Morphogenetic Proteins
NF-kappa B
T-Box Domain Proteins
Tbx20 protein, mouse
Transcription Factors
I-kappa B Kinase