Novel zinc finger transcription factor ZFP580 promotes differentiation of bone marrow-derived endothelial progenitor cells into endothelial cells via eNOS/NO pathway

Wei, Shuping; Huang, Jiawen; Li, Yuming; Zhao, Juan; Luo, Yang; Meng, Xiangyan; Sun, Huiyan; Zhou, Xin; Zhang, Mei; Zhang, Wencheng

doi:10.1016/j.yjmcc.2015.08.004

Cited by 18 publications

(18 citation statements)

References 36 publications

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“…Furthermore, it was also reported that ATRA activated SM22a expression through KLF4 binding to its ciselements in an acetylation-dependent manner and inhibited VSMC differentiation [14]. Our previous studies have shown that the novel zinc-finger transcription factor ZFP580 plays important roles in endothelial biology and cardiovascular disease [24][25][26]. We then evaluated the role of ZFP580 in VSMC biology using both gain-and loss-of-function analyses.…”

Section: Discussionmentioning

confidence: 97%

“…The expression of ZFP580 significantly changed in VSMCs with intimal neovascularization. In addition, ZFP580 plays an important regulatory role in EPC-EC differentiation via the eNOS/NO pathway [25,26]. Therefore, we hypothesized that ZFP580 might play an important role in the process of VSMC phenotypic switching and could be used as a new molecular target for treating such diseases.…”

Section: Introductionmentioning

confidence: 99%

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Novel Zinc Finger Transcription Factor ZFP580 Facilitates All-Trans Retinoic Acid -Induced Vascular Smooth Muscle Cells Differentiation by Rarα-Mediated PI3K/Akt and ERK Signaling

Wei

Zhang

Han

et al. 2018

Cell Physiol Biochem

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Background/Aims: Phenotypic switching of vascular smooth muscle cells (VSMC) plays a vital role in the development of vascular diseases. All-trans retinoic acid (ATRA) is known to regulate VSMC phenotypes. However, the underlying mechanisms remain completely unknown. Here, we have investigated the probable roles and underlying mechanisms of the novel C2H2 zinc finger transcription factor ZFP580 on ATRA-induced VSMC differentiation. Methods: VSMCs were isolated, cultured, and identified. VSMCs were infected with an adenovirus encoding ZFP580 or Ad-siRNA to silence ZFP580. The expression levels of ZFP580, SMα-actin, SM22α, SMemb, RARα, RARβ, and RARγ were assayed by Q-PCR and western blot. A rat carotid artery injury model and morphometric analysis of intimal thickening were also used in this study. Results: ATRA caused a significant reduction of VSMC proliferation and migration in a doseand time-dependent manner. Moreover, it promoted VSMC differentiation by enhancing expression of differentiation markers and reducing expression of dedifferentiation markers. This ATRA activity was accompanied by up-regulation of ZFP580, with concomitant increases in RARα expression. In contrast, silencing of the RARα gene or inhibiting RARα with its antagonist Ro41-5253 abrogated the ATRA-induced ZFP580 expression. Furthermore, ATRA binding to RARα induced ZFP580 expression via the PI3K/Akt and ERK pathways. Adenovirusmediated overexpression of ZFP580 promoted VSMC differentiation by enhancing expression of SM22α and SMα-actin and reducing expression of SMemb. In contrast, silencing ZFP580 dramatically reduced the expression of differentiation markers and increased expression of dedifferentiation markers. The classic rat carotid artery balloon injury model demonstrated that ZFP580 inhibited proliferation and intimal hyperplasia in vivo. Conclusion: The novel zinc finger transcription factor ZFP580 facilitates ATRA-induced VSMC differentiation by the RARα-mediated PI3K/Akt and ERK signaling pathways. This might represent a novel mechanism of regulation of ZFP580 by ATRA and RARα, which is critical for understanding the biological functions of retinoids during VSMC phenotypic modulation.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Novel Zinc Finger Transcription Factor ZFP580 Facilitates All-Trans Retinoic Acid -Induced Vascular Smooth Muscle Cells Differentiation by Rarα-Mediated PI3K/Akt and ERK Signaling

Wei

Zhang

Han

et al. 2018

Cell Physiol Biochem

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“…In our previous work, ZNF580 plays important roles in the migration and proliferation of endothelial cells (Sun et al, ; Ren et al, ; Luo et al, ) and differentiation of endothelial progenitor cells into endothelial cells (Wei et al, ). By using Targetscan software, we predicted that miR‐206 can modulate expression of ZFP580.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous works show that ZNF580 mediates S1P/p38MAPK signaling to promote endothelial cell migration and proliferation (Sun and Wei, 2010) and the mPEG-b-P(MMD-co-GA)-g-PEI based microparticles could be a suitable non-viral gene carrier for ZNF580 gene to enhance rapid endothelialization (Shi et al, 2014a). Furthermore, ZFP580 can promote differentiation of bone marrow-derived endothelial progenitor cells into endothelial cells (Wei and Huang, 2015). It is suggested that ZFP580 plays a divergent role in endothelial and smooth muscle cell biology.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐206 regulates vascular smooth muscle cell phenotypic switch and vascular neointimal formation

Sun

Cai

Zhang

et al. 2017

Cell Biology International

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MiR-206 has been found to play a critical role in skeletal muscle proliferation, differentiation, and regeneration. However, little is known about the function of miR-206 in vascular smooth muscle cells (VSMCs) biology. In this study, we will investigate its roles in phenotypic switching of VSMCs and neointimal lesion formation. First, we identified the expression of miR-206 in VSMCs treated with various concentrations of TGFβ1 and in rat carotid arteries after angioplasty by using qPCR. TGFβ1 inhibited the expression of miR-206 and TGFβ1 inhibitor induced miR-206 expression. In VSMCs of injured vascular walls, miR-206 expression was upregulated. Then, we overexpressed miR-206 using lentivirus Lv-rno-mir-206 and knocked down miR-206 using LV-rno-mir-206-inhibitor in rat carotid arteries after angioplasty. Overexpression of miR-206 resulted in decreasing SM22α expression in VSMCs in vitro and knockdown of miR-206 suppressed neointimal lesion formation in vivo. Finally, ZFP580 (zinc finger protein 580) was identified as the direct target of miR-206 in VSMCs by using luciferase report assay. The results indicate that miR-206 is involved in phenotypic switching of VSMCs and neointimal lesion formation after angioplasty through targeting ZFP580. These findings may provide a novel therapeutic target in post-angioplasty restenosis.

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“…EPCs participate in the process of endothelium repair through differentiation to ECS (29). To date, numerous studies have focused on the transcription factors active during EPC differentiation under static conditions (30)(31)(32). EPCs, which are located primarily in the bone marrow and peripheral blood, are transported to the injury area through blood circulation (33).…”

Section: Discussionmentioning

confidence: 99%

Function of Kr�ppel‑like factor 2 in the shear stress‑induced cell differentiation of endothelial progenitor cells to endothelial cells

et al. 2019

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The present study aimed to evaluate the effects of Krüppel-like factor 2 (KLF2) on the differentiation of endothelial progenitor cells (EPCs) to endothelial cells (ECs) induced by shear stress, and to investigate the corresponding mechanisms. Cultured rat late EPCs were exposed to shear stress (12 dyn/cm 2) for different lengths of time. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to measure the initial KLF2 mRNA levels in each group. Subsequently, the EPCs were treated with anti-integrin β1 or β3 antibodies to block integrin β1 and β3, respectively, or cytochalasin D to destroy F-actin, and the subsequent expression levels of KLF2 in EPCs were measured. Then, KLF2 small interfering RNAs (siRNAs) were transfected into EPCs, and RT-qPCR was used to measure the mRNA expression level of KLF2. Additionally, flow cytometry was applied to evaluate the protein levels of cluster of differentiation 31 (CD31) and the von Willebrand factor (vWF), and the regulatory effects of KLF2 in the promoter region of vWF were determined via a luciferase assay. High shear stress upregulated KLF2 expression, while blocking integrin β1/β3 or destroying F-actin resulted in a corresponding decrease in KLF2 expression. Downregulation of KLF2 expression by siKLF2 inhibited the differentiation of EPCs to ECs under shear stress conditions, while the expression of EC-specific markers decreased, including CD31 and vWF. Various lengths of the vWF promoter region induced vWF expression, and EPCs co-transfected with KLF2 significantly increased the vWF expression levels compared with the group treated with vWF alone (P<0.01). In conclusion, shear stress may upregulate KLF2 expression, which may be associated with the integrin-actin cytoskeleton system. Most importantly, the shear stress-induced differentiation of EPCs may be mediated by KLF2.

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Novel zinc finger transcription factor ZFP580 promotes differentiation of bone marrow-derived endothelial progenitor cells into endothelial cells via eNOS/NO pathway

Cited by 18 publications

References 36 publications

Novel Zinc Finger Transcription Factor ZFP580 Facilitates All-Trans Retinoic Acid -Induced Vascular Smooth Muscle Cells Differentiation by Rarα-Mediated PI3K/Akt and ERK Signaling

Novel Zinc Finger Transcription Factor ZFP580 Facilitates All-Trans Retinoic Acid -Induced Vascular Smooth Muscle Cells Differentiation by Rarα-Mediated PI3K/Akt and ERK Signaling

MicroRNA‐206 regulates vascular smooth muscle cell phenotypic switch and vascular neointimal formation

Function of Kr�ppel‑like factor 2 in the shear stress‑induced cell differentiation of endothelial progenitor cells to endothelial cells

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