Acute mitochondrial damage and the energy crisis following axonal injury highlight mitochondrial transport as an important target for axonal regeneration.Syntaphilin(Snph),known for its potent mitochondrial anchoring ...Acute mitochondrial damage and the energy crisis following axonal injury highlight mitochondrial transport as an important target for axonal regeneration.Syntaphilin(Snph),known for its potent mitochondrial anchoring action,has emerged as a significant inhibitor of both mitochondrial transport and axonal regeneration.Therefore,investigating the molecular mechanisms that influence the expression levels of the snph gene can provide a viable strategy to regulate mitochondrial trafficking and enhance axonal regeneration.Here,we reveal the inhibitory effect of microRNA-146b(miR-146b)on the expression of the homologous zebrafish gene syntaphilin b(snphb).Through CRISPR/Cas9 and single-cell electroporation,we elucidated the positive regulatory effect of the miR-146b-snphb axis on Mauthner cell(M-cell)axon regeneration at the global and single-cell levels.Through escape response tests,we show that miR-146b-snphb signaling positively regulates functional recovery after M-cell axon injury.In addition,continuous dynamic imaging in vivo showed that reprogramming miR-146b significantly promotes axonal mitochondrial trafficking in the pre-injury and early stages of regeneration.Our study reveals an intrinsic axonal regeneration regulatory axis that promotes axonal regeneration by reprogramming mitochondrial transport and anchoring.This regulation involves noncoding RNA,and mitochondria-associated genes may provide a potential opportunity for the repair of central nervous system injury.展开更多
Objective Vascular smooth muscle cell(VSMC)differentiation from stem cells is one source of the increasing number of VSMCs that are involved in vascular remodeling-related diseases such as hypertension,atherosclerosis...Objective Vascular smooth muscle cell(VSMC)differentiation from stem cells is one source of the increasing number of VSMCs that are involved in vascular remodeling-related diseases such as hypertension,atherosclerosis,and restenosis.MicroRNA-146a(miR-146a)has been proven to be involved in cell proliferation,migration,and tumor metabolism.However,little is known about the functional role of miR-146a in VSMC differentiation from embryonic stem cells(ESCs).This study aimed to determine the role of miR-146a in VSMC differentiation from ESCs.Methods Mouse ESCs were differentiated into VSMCs,and the cell extracts were analyzed by Western blotting and RT-qPCR.In addition,luciferase reporter assays using ESCs transfected with miR-146a/mimic and plasmids were performed.Finally,C57BL/6J female mice were injected with mimic or miR-146a-overexpressing ESCs,and immunohistochemistry,Western blotting,and RT-qPCR assays were carried out on tissue samples from these mice.Results miR-146a was significantly upregulated during VSMC differentiation,accompanied with the VSMC-specific marker genes smooth muscle-alpha-actin(SMαA),smooth muscle 22(SM22),smooth muscle myosin heavy chain(SMMHC),and h1-calponin.Furthermore,overexpression of miR-146a enhanced the differentiation process in vitro and in vivo.Concurrently,the expression of Kruppel-like factor 4(KLF4),predicted as one of the top targets of miR-146a,was sharply decreased in miR-146a-overexpressing ESCs.Importantly,inhibiting KLF4 expression enhanced the VSMC-specific gene expression induced by miR-146a overexpression in differentiating ESCs.In addition,miR-146a upregulated the mRNA expression levels and transcriptional activity of VSMC differentiation-related transcription factors,including serum response factor(SRF)and myocyte enhancer factor 2c(MEF-2c).Conclusion Our data support that miR-146a promotes ESC-VSMC differentiation through regulating KLF4 and modulating the transcription factor activity of VSMCs.展开更多
背景:正常骨代谢有赖于成骨细胞介导的骨形成与破骨细胞介导的骨吸收之间的平衡,破坏该平衡会引发骨代谢相关疾病。微小RNA-146a(miR-146a)是一种非编码小分子RNA,在骨代谢中发挥重要作用。目的:就微小RNA-146a调控骨代谢的分子机制及...背景:正常骨代谢有赖于成骨细胞介导的骨形成与破骨细胞介导的骨吸收之间的平衡,破坏该平衡会引发骨代谢相关疾病。微小RNA-146a(miR-146a)是一种非编码小分子RNA,在骨代谢中发挥重要作用。目的:就微小RNA-146a调控骨代谢的分子机制及其在骨组织工程中的应用做一综述。方法:作者于2025年4月对中国知网、PubMed和Web of Science数据库中2000年1月至2025年4月发表的相关文献进行检索,中文检索词为“微小RNA-146a,骨,骨代谢,成骨细胞,破骨细胞,骨组织再生”;英文检索词为“microRNA-146a,Bone metabolism,Osteoblast,Osteoclast,Bone regeneration”,检索文献类型不限。共检索到文献11230篇,其中中国知网检索到中文文献988篇,PubMed数据库检索到英文文献5952篇,Web of Science数据库检索到英文文献4290篇。目标纳入研究骨代谢过程及其影响因素的相关文献,探究微小RNA-146a如何调控骨代谢过程、骨代谢关键细胞生物学行为的相关文献,微小RNA-146a应用于维持骨稳态、促进骨组织修复再生的相关文献;排除与文章主题相关度低、内容较陈旧、实验设计不严密、研究结果可信度较差、论证不充分的文献。最终根据文献排除标准筛选出与该综述主题密切相关且研究新颖、数据真实可信、论证充分、具有临床应用价值的90篇文献进行综述。结果与结论:①微小RNA-146a可通过抑制Wnt、Smad4、沉默信息调节因子2相关酶1等基因表达抑制成骨细胞形成及活性,或通过抑制肿瘤坏死因子受体相关因子6、白细胞介素1受体相关激酶1基因表达抑制破骨细胞形成,也可调节成骨细胞与破骨细胞的相互作用;②微小RNA-146a的异常表达可使成骨细胞和破骨细胞功能失调,打破骨代谢平衡,引发骨质疏松、骨关节炎、牙周炎等骨代谢相关疾病;③因此,微小RNA-146a可作为骨代谢相关疾病诊疗的潜在靶点,在骨代谢相关疾病治疗和骨组织工程中具有一定的应用前景。展开更多
基金supported by the core facility Center for Life Sciences,University of Science and Technology of China,Research Funds of the Center for Advanced Interdisciplinary Science and Biomedicine of IHM(QYZD20220002)the National Natural Science Foundation of China(82071357)the Ministry of Science and Technology of China(2019YFA0405600).
文摘Acute mitochondrial damage and the energy crisis following axonal injury highlight mitochondrial transport as an important target for axonal regeneration.Syntaphilin(Snph),known for its potent mitochondrial anchoring action,has emerged as a significant inhibitor of both mitochondrial transport and axonal regeneration.Therefore,investigating the molecular mechanisms that influence the expression levels of the snph gene can provide a viable strategy to regulate mitochondrial trafficking and enhance axonal regeneration.Here,we reveal the inhibitory effect of microRNA-146b(miR-146b)on the expression of the homologous zebrafish gene syntaphilin b(snphb).Through CRISPR/Cas9 and single-cell electroporation,we elucidated the positive regulatory effect of the miR-146b-snphb axis on Mauthner cell(M-cell)axon regeneration at the global and single-cell levels.Through escape response tests,we show that miR-146b-snphb signaling positively regulates functional recovery after M-cell axon injury.In addition,continuous dynamic imaging in vivo showed that reprogramming miR-146b significantly promotes axonal mitochondrial trafficking in the pre-injury and early stages of regeneration.Our study reveals an intrinsic axonal regeneration regulatory axis that promotes axonal regeneration by reprogramming mitochondrial transport and anchoring.This regulation involves noncoding RNA,and mitochondria-associated genes may provide a potential opportunity for the repair of central nervous system injury.
基金funded by the National Natural Science Foundation of China(No.82070376 and No.81873491)the Natural Science Foundation of Zhejiang Province(No.LY21H020005)+1 种基金the Zhejiang Medical Science and Technology Project(No.2019KY376 and No.2018KY071)a Ningbo Science and Technology Project(No.202002N3173).
文摘Objective Vascular smooth muscle cell(VSMC)differentiation from stem cells is one source of the increasing number of VSMCs that are involved in vascular remodeling-related diseases such as hypertension,atherosclerosis,and restenosis.MicroRNA-146a(miR-146a)has been proven to be involved in cell proliferation,migration,and tumor metabolism.However,little is known about the functional role of miR-146a in VSMC differentiation from embryonic stem cells(ESCs).This study aimed to determine the role of miR-146a in VSMC differentiation from ESCs.Methods Mouse ESCs were differentiated into VSMCs,and the cell extracts were analyzed by Western blotting and RT-qPCR.In addition,luciferase reporter assays using ESCs transfected with miR-146a/mimic and plasmids were performed.Finally,C57BL/6J female mice were injected with mimic or miR-146a-overexpressing ESCs,and immunohistochemistry,Western blotting,and RT-qPCR assays were carried out on tissue samples from these mice.Results miR-146a was significantly upregulated during VSMC differentiation,accompanied with the VSMC-specific marker genes smooth muscle-alpha-actin(SMαA),smooth muscle 22(SM22),smooth muscle myosin heavy chain(SMMHC),and h1-calponin.Furthermore,overexpression of miR-146a enhanced the differentiation process in vitro and in vivo.Concurrently,the expression of Kruppel-like factor 4(KLF4),predicted as one of the top targets of miR-146a,was sharply decreased in miR-146a-overexpressing ESCs.Importantly,inhibiting KLF4 expression enhanced the VSMC-specific gene expression induced by miR-146a overexpression in differentiating ESCs.In addition,miR-146a upregulated the mRNA expression levels and transcriptional activity of VSMC differentiation-related transcription factors,including serum response factor(SRF)and myocyte enhancer factor 2c(MEF-2c).Conclusion Our data support that miR-146a promotes ESC-VSMC differentiation through regulating KLF4 and modulating the transcription factor activity of VSMCs.
文摘背景:正常骨代谢有赖于成骨细胞介导的骨形成与破骨细胞介导的骨吸收之间的平衡,破坏该平衡会引发骨代谢相关疾病。微小RNA-146a(miR-146a)是一种非编码小分子RNA,在骨代谢中发挥重要作用。目的:就微小RNA-146a调控骨代谢的分子机制及其在骨组织工程中的应用做一综述。方法:作者于2025年4月对中国知网、PubMed和Web of Science数据库中2000年1月至2025年4月发表的相关文献进行检索,中文检索词为“微小RNA-146a,骨,骨代谢,成骨细胞,破骨细胞,骨组织再生”;英文检索词为“microRNA-146a,Bone metabolism,Osteoblast,Osteoclast,Bone regeneration”,检索文献类型不限。共检索到文献11230篇,其中中国知网检索到中文文献988篇,PubMed数据库检索到英文文献5952篇,Web of Science数据库检索到英文文献4290篇。目标纳入研究骨代谢过程及其影响因素的相关文献,探究微小RNA-146a如何调控骨代谢过程、骨代谢关键细胞生物学行为的相关文献,微小RNA-146a应用于维持骨稳态、促进骨组织修复再生的相关文献;排除与文章主题相关度低、内容较陈旧、实验设计不严密、研究结果可信度较差、论证不充分的文献。最终根据文献排除标准筛选出与该综述主题密切相关且研究新颖、数据真实可信、论证充分、具有临床应用价值的90篇文献进行综述。结果与结论:①微小RNA-146a可通过抑制Wnt、Smad4、沉默信息调节因子2相关酶1等基因表达抑制成骨细胞形成及活性,或通过抑制肿瘤坏死因子受体相关因子6、白细胞介素1受体相关激酶1基因表达抑制破骨细胞形成,也可调节成骨细胞与破骨细胞的相互作用;②微小RNA-146a的异常表达可使成骨细胞和破骨细胞功能失调,打破骨代谢平衡,引发骨质疏松、骨关节炎、牙周炎等骨代谢相关疾病;③因此,微小RNA-146a可作为骨代谢相关疾病诊疗的潜在靶点,在骨代谢相关疾病治疗和骨组织工程中具有一定的应用前景。
