RGMa promotes dedifferentiation of vascular smooth muscle cells into a macrophage-like phenotype in vivo and in vitro

Yuan, Xiaofan; Xiao, Hongmei; Hu, Qingzhe; Shen, Guanru; Qin, Xinyue

doi:10.1016/j.jlr.2022.100276

Cited by 7 publications

(6 citation statements)

References 38 publications

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“…Primary VSMCs were isolated from rat aortas as previously described (Yuan et al, 2022). VSMCs were cultured in Dulbecco's modified Eagle medium (DMEM) (catalog no.…”

Section: Methodsmentioning

confidence: 99%

“…The efficiency of the LV-shKLF13 was detected by autofluorescence and Western blotting. Primary VSMCs were isolated from rat aortas as previously described (Yuan et al, 2022). VSMCs were cultured in Dulbecco's modified Eagle medium (DMEM) (catalog no.…”

Section: Carotid Lentivirus Interventionmentioning

confidence: 99%

“…Primary rat VSMCs and arterial sections were collected for IF staining, as described previously (Yuan et al, 2022). Samples were incubated with primary antibodies against KLF13 (1:100 dilution; catalog no.…”

Section: Immunofluorescence (If)mentioning

confidence: 99%

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KLF13 promotes VSMCs phenotypic dedifferentiation by directly binding to the SM22α promoter

Yuan,

Jiang,

Xue

et al. 2024

Journal Cellular Physiology

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Krüppel‐like factor 13 (KLF13), a zinc finger transcription factor, is considered as a potential regulator of cardiomyocyte differentiation and proliferation during heart morphogenesis. However, its precise role in the dedifferentiation of vascular smooth muscle cells (VSMCs) during atherosclerosis and neointimal formation after injury remains poorly understood. In this study, we investigated the relationship between KLF13 and SM22α expression in normal and atherosclerotic plaques by bioanalysis, and observed a significant increase in KLF13 levels in the atherosclerotic plaques of both human patients and ApoE−/− mice. Knockdown of KLF13 was found to ameliorate intimal hyperplasia following carotid artery injury. Furthermore, we discovered that KLF13 directly binds to the SM22α promoter, leading to the phenotypic dedifferentiation of VSMCs. Remarkably, we observed a significant inhibition of platelet‐derived growth factor BB‐induced VSMCs dedifferentiation, proliferation, and migration when knocked down KLF13 in VSMCs. This inhibitory effect of KLF13 knockdown on VCMC function was, at least in part, mediated by the inactivation of p‐AKT signaling in VSMCs. Overall, our findings shed light on a potential therapeutic target for treating atherosclerotic lesions and restenosis after vascular injury.

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“…Primary VSMCs were isolated from rat aortas as previously described (Yuan et al, 2022). VSMCs were cultured in Dulbecco's modified Eagle medium (DMEM) (catalog no.…”

Section: Methodsmentioning

confidence: 99%

Section: Carotid Lentivirus Interventionmentioning

confidence: 99%

See 1 more Smart Citation

KLF13 promotes VSMCs phenotypic dedifferentiation by directly binding to the SM22α promoter

Yuan,

Jiang,

Xue

et al. 2024

Journal Cellular Physiology

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“…In addition, several vital organs, including the heart, lung, liver, kidney and spleen, were harvested at corresponding sacrifice time points, and H&E staining was used to examine the organizational structures of these organs to validate the in vivo biosafety of the biohybrid hydrogel scaffolds after implantation [23,26]. More importantly, immunofluorescent CD31, F4/80 and CD3 staining were used to evaluate the neovascularization and macrophage and lymphocyte infiltration of the extracted hydrogel scaffolds, respectively, according to previously reported protocols [24,33,34]. In brief, prepared slices were dehydrated sufficiently using xylene and graded ethanol (100%, 85% and 75%), then, blocking of nonspecific proteins was conducted using 3% BSA solution after antigen retrieval at room temperature for 30 min prior to the incubation of antibodies.…”

Section: Histological Evaluation and In Vivo Biosafetymentioning

confidence: 99%

Graphene oxide/copper nanosheet-integrated hydrogel platform as a bioactive and biocompatible scaffold to accelerate calvarial defect restoration

Yang,

Zhou,

et al. 2023

Preprint

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Background The treatment of craniofacial bone defects caused by trauma, tumors, and infectious and degenerative diseases is a significant issue in current clinical practice. Following the rapid development of bone tissue engineering (BTE) in the last decade, bioactive scaffolds coupled with multifunctional properties are in high demand with regard to effective therapy for bone defects. Methods In this study, motivated by the versatile biological functions of nanomaterials and synthetic hydrogels, copper nanoparticle (CuNP)-decorated graphene oxide (GO) nanosheets (GO/Cu) were combined with methacrylated gelatin (GelMA)-based organic-inorganic hybrids to construct porous bone scaffolds that mimic the extracellular matrix (ECM) of bone tissues by photocrosslinking. The material characterizations, in vitro cytocompatibility and osteogenesis of the biohybrid hydrogel scaffolds were investigated, and two different animal models were established to further confirm the in vivo neovascularization, macrophage recruitment, biocompatibility, biosafety and bone regenerative potential. Results It found that GO/Cu-functionalized GelMA/β-TCP hydrogel scaffolds exhibited evidently promoted osteogenic activities and excellent cytocompatibility, with favorable surface characteristics and sustainable release of Cu2+. Additionally, improved neovascularization, macrophage recruitment and tissue integration were found in mice implanted with the bioactive hydrogels. More importantly, the observations of microCT reconstruction and histological analysis in a calvarial bone defect model in rats treated with GO/Cu-incorporated hydrogel scaffolds, demonstrated significantly accelerated bone healing. Conclusions Taken together, this BTE-based bone repair strategy provides a promising and feasible method for constructing multifunctional GO/Cu nanocomposite- incorporated biohybrid hydrogel scaffolds with facilitated osteogenesis, angiogenesis and immunoregulation in one system, thereby demonstrating the great application potential for correcting craniofacial bone defects in future clinical scenarios.

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“…Importantly, the activity of ERK1/2 increases via ECM receptors and ECM ligands ( Sheng et al, 2017 ; Ohkuro et al, 2018 ; Olea-Flores et al, 2019 ), and thus ERK1/2 activity could represent a key signaling node to adjust cell outcome to ECM status ( Anerillas et al, 2020 ). The evidence that ERK1/2 activate EMT core transcription factors like SNAIL, SLUG, TWIST, ZEB1, and ZEB2 ( Weiss et al, 2012 ; Strippoli et al, 2015 ; Chiu et al, 2017 ; Sinh et al, 2017 ; Yuan et al, 2022 ) is mainly obtained from cancer cell studies.…”

Section: Mapks In Senescent Cell Fate Decisionsmentioning

confidence: 99%

MAPKs in the early steps of senescence implemEMTation

Anerillas

Altés

Gorospe

2023

Front. Cell Dev. Biol.

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Evidence is accumulating that the earliest stages of the DNA damage response can direct cells toward senescence instead of other cell fates. In particular, tightly regulated signaling through Mitogen-Activated Protein Kinases (MAPKs) in early senescence can lead to a sustained pro-survival program and suppress a pro-apoptotic program. Importantly, an epithelial-to-mesenchymal Transition (EMT)-like program appears essential for preventing apoptosis and favoring senescence following DNA damage. In this review, we discuss how MAPKs might influence EMT features to promote a senescent phenotype that increases cell survival at the detriment of tissue function.

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RGMa promotes dedifferentiation of vascular smooth muscle cells into a macrophage-like phenotype in vivo and in vitro

Cited by 7 publications

References 38 publications

KLF13 promotes VSMCs phenotypic dedifferentiation by directly binding to the SM22α promoter

KLF13 promotes VSMCs phenotypic dedifferentiation by directly binding to the SM22α promoter

Graphene oxide/copper nanosheet-integrated hydrogel platform as a bioactive and biocompatible scaffold to accelerate calvarial defect restoration

MAPKs in the early steps of senescence implemEMTation

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