title: Enhancement of early cardiac differentiation of dedifferentiated fat cells by dimethyloxalylglycine via notch signaling pathway.
abstract: Background:Hypoxia has been reported to possess the ability to induce mature lipid-filled adipocytes to differentiate into fibroblast-like multipotent dedifferentiated fat (DFAT) cells and stem cells such as iPSCs (interstitial pluripotent stem cells) and ESCs (embryonic stem cells) and then to differentiate into cardiomyocytes. However, the effect of hypoxia on cardiac differentiation of DFAT cells and its underlying molecular mechanism remains to be investigated.Objective:To investigate the role of hypoxia in early cardiac differentiation of DFAT cells and the underlying molecular mechanism.Methods:DFAT cells were prepared from 4 to 6 week-age mice and cultured under hypoxic conditions by adding Prolyl hydroxylase inhibitor and dimethyloxalylglycine (DMOG) into the culture media. To inhibit or block Notch signaling, γ-secretase inhibitor-II (GSI-II) and Notch1 siRNA (si-Notch1) were used. DFAT cell viability was detected using MTT assay. qRT-PCR, immunofluorescence microscopy and western blotting were used to evaluate the cardiac differentiation of DFAT cells and co-immunoprecipitation was used to study the interaction between HIF-1α and Notch signaling.Results:0.6-mM DMOG failed to affect the viability of DFAT cells, but stimulated the cells to express early cardiac transcription factors including Islet1, Nkx2.5 and Gata4 in a time-dependent manner and increase the number of cTnT+cardiomyocytes (detected at the 28thday after stimulation). It was also demonstrated that DMOG was involved in HIF-1α and Notch signaling as well as HIF-1α-NICD complex formation.Conclusion:Hypoxia enhanced early cardiac differentiation of DFAT cells through HIF-1α and Notch signaling pathway.
authors.affiliation: Guizhou Institute for Cardiovascular DiseaseGuiyang 550002, China; Department of Cardiology, Guizhou Province People's HospitalGuiyang 550002, China.
authors.forename: Fuhai
authors.initials: F
authors.lastname: Li
authors.affiliation: Guizhou Institute for Cardiovascular DiseaseGuiyang 550002, China; Department of Cardiology, Guizhou Province People's HospitalGuiyang 550002, China.
authors.forename: Zongzhuang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Guizhou Institute for Cardiovascular DiseaseGuiyang 550002, China; Department of Cardiology, Guizhou Province People's HospitalGuiyang 550002, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Guizhou Institute for Cardiovascular DiseaseGuiyang 550002, China; Department of Cardiology, Guizhou Province People's HospitalGuiyang 550002, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Emergency Department, Qingdao Municipal Hospital Qingdao 266011, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pathology, Guizhou Province People's Hospital Guiyang 550002, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yi
authors.affiliation: Guizhou Institute for Cardiovascular DiseaseGuiyang 550002, China; Department of Cardiology, Guizhou Province People's HospitalGuiyang 550002, China.
authors.forename: Chenyun
authors.initials: C
authors.lastname: Zhang
keywords: Dedifferentiated fat cell; hypoxia; notch signaling pathway