Stem Cell Research & Therapy
·
2025
·Vol. 16
·期 1
·1-17
·
IF 7.3
Du Dongdong,Wang Ting,Sun Yaodong,Zhang Yi,Zhang Bufan,Shao Jingrong,Yang Mengxue,Huang Chuan,Zuo Shengkai,Wu Naishi
Background The poor viability and paracrine function of transplanted mesenchymal stem cells (MSCs) hamper their therapeutic efficacy in ischemic heart injury treatment. Protein arginine methyltransferases (PRMTs) mediate arginine methylation and have important functions in cellular responses. However, the role of PRMTs in MSC-based therapies for ischemic heart injury remains unclear. The aim of this study was to investigate the effect of PRMT1 on MSC function and therapeutic efficacy using a mouse myocardial infarction (MI) model.Methods We isolated, cultured, and identified mouse adipose tissue-derived mesenchymal stromal cells (ADSCs). We used Furamidine, a PRMT1 inhibitor, and adenoviral shPRMT1 to study the effects of PRMT1 inhibition on ADSC proliferation, migration, and viability. We performed RNA sequencing and biochemical experiments to elucidate the molecular mechanisms of PRMT1 in ADSCs. Finally, we infected ADSCs with adenoviral shPRMT1 and administered an intramyocardial injection after MI. Cardiac function was evaluated using echocardiography and pathological staining, and ADSCs survival rates, cardiomyocyte apoptosis, and capillary density were evaluated using immunofluorescence staining.Results We found that PRMT1 was highly expressed in ADSCs and markedly upregulated in response to H2O2 challenge. Inhibition of PRMT1 by Furamidine or adenoviral shPRMT1 promoted ADSC proliferation and migration and reduced H2O2-induced ADSCs apoptosis. Mechanistically, PRMT1 inhibition significantly increased the expression of matrix metallopeptidase (MMP)-10, placenta growth factor (PlGF) and transforming growth factor (TGF)-β2 in ADSCs through transcription factor RUNX1. Blockage of RUNX1 abolished the proliferative and migratory effects of PRMT1 inhibition in ADSCs. Compared to ADSCs infected with the adenovirus-control, PRMT1 knockdown adenovirus markedly increased the survival and retention of transplanted ADSCs in injured hearts after MI. ADSCs with PRMT1 knockdown markedly improved cardiac function and alleviated cardiac fibrosis in mice after MI by reducing cardiomyocyte apoptosis and increasing capillary density.Conclusion sPRMT1 inhibition enhances the cardioprotective effect of ADSCs against MI through RUNX1-mediated production of MMP-10/PlGF/TGF-β2. Overall, PRMT1 inhibition is a promising strategy for augmenting MSCs therapeutic efficacy in ischemic cardiomyopathy.
研究领域:
心血管医学
·
分子生物学
·
干细胞研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Open Medicine
·
2023
·Vol. 18
·期 1
·
IF 2.1
Yangfa Chao,Wenting Huang,Zhiheng Xu,Ping Li,Shaodong Gu
Lymphocyte apoptosis is a latent factor for immunosuppression in sepsis. Forkhead box protein P3 (FOXP3) can interact with RUNX family transcription factor 1 (RUNX1) in regulatory T cells. Our research was to probe whether RUNX1/FOXP3 axis affects immunosuppression in the process of sepsis by modulating T and B lymphocyte apoptosis. We constructed sepsis model in mice and mouse CD4 + T and CD19 + B lymphocytes. RUNX1 and FOXP3 expressions and apoptosis in cells were assessed by western blot, quantitative real-time PCR, and flow cytometer. Inflammation of serum and pathological damage was assessed by ELISA and H&E staining. Relationship between RUNX1 and FOXP3 was assessed by co-immunoprecipitation. The findings showed that RUNX1 ameliorated the survival rate, pathological damage, and decreased inflammation-related factors, and inhibited apoptosis of CD4 + T and CD19 + B cells in cecal ligation and puncture mice. Furthermore, RUNX1 up-regulated the viability and down-regulated apoptotic rate with the changed expressions of apoptosis-related molecules in lipopolysaccharide (LPS)-mediated CD4 + T and CD19 + B cells. Additionally, FOXP3 interacted with RUNX1, and its silencing decreased RUNX1 expression and reversed the inhibitory effect of RUNX1 on apoptosis of LPS-mediated CD4 + T and CD19 + B cells. In summary, the RUNX1/FOXP3 axis alleviated immunosuppression in sepsis progression by weakening T and B lymphocyte apoptosis.
研究领域:
免疫学
·
分子生物学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL CYCLE
·
2021
·
IF 4.534
Jun Zhu,Qiwei Fu,Jiahua Shao,Jinhui Peng,Qirong Qian,Yiqin Zhou,Yi Chen
This study explored the role of MEG3 in the cartilage differentiation of bone marrow mesenchymal stem cells (BMSCs). We investigated the effects of over-expression and knockdown of MEG3 on cell viability, cell differentiation, and the expressions of MEG3, miR-129-5p, COL2, chondrocyte differentiation-related genes (sry-type high-mobility-group box 9 (SOX9), SOX5, Aggrecan, silent information regulator 1 (SIRT1), and Cartilage oligomeric matrix protein (COMP)). The targeting relationship between MEG3 and miR-129-5p and the target gene of miR-129-5p was confirmed through Starbase, TargetScan and luciferase experiments. Finally, a series of rescue experiments were conducted to study the regulatory effects of MEG3 and miR-129-5p. BMSCs were identified as CD29+ and CD44+ positive, and their differentiation was time-dependent. As BMSCs differentiated, MEG3 expression was up-regulated, but miR-129-5p was down-regulated. Over-expressed MEG3 promoted the viability and differentiation of BMSCs, up-regulated the expressions of COL2 and chondrocyte differentiation-related genes, and inhibited miR-129-5p. Runt-related transcription factor 1 (RUNX1) was negatively regulated as a target gene of miR-129-5p. Results of rescue experiments showed that the inhibitory effect of miR-129-5p mimic on BMSCs could be partially reversed by MEG3. Over-expression of MEG3 regulated the miR-129-5p/RUNX1 axis to promote the differentiation of BMSCs into chondrocytes. This study provides a reliable basis for the application of lncRNA in articular cartilage injury.
研究领域:
干细胞生物学
·
分子生物学
·
再生医学
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2024
·Vol. 479
·期 7
·1747-1766
·
IF 3.5
Wang Qun,Lu Weijun,Lu Li,Wu Ruopu,Wu Dongde
Receptor interacting protein serine/threonine kinase 4 (RIPK4) is widely involved in human cancer development. Nevertheless, its role in colon cancer (COAD) has not been elucidated till now. Our research aimed at exploring the function and underlying molecular mechanism of RIPK4 in COAD progression. Through bioinformatic analyses and RT-qPCR, RIPK4 was discovered to be increased in COAD cells and tissues, and its high level predicted poor prognosis. Loss-of-function assays revealed that RIPK4 silencing suppressed COAD cell growth, induced cell cycle arrest, and enhanced cell apoptosis. In vivo experiments also proved that tumor growth was inhibited by silencing of RIPK4. Luciferase reporter assay validated that RIPK4 was targeted and negatively regulated by miR-575. Western blotting demonstrated that Wnt3a, phosphorylated (p)-GSK-3β, and cytoplasmic and nuclear β-catenin protein levels, β-catenin nuclear translocation, and Cyclin D1, CDK4, Cyclin E, and c-Myc protein levels were reduced by RIPK4 knockdown, which however was reversed by treatment with LiCl, the Wnt/β-catenin pathway activator. LiCl also offset the influence of RIPK4 knockdown on COAD cell growth, cell cycle process, and apoptosis. Finally, RIPK4 downregulation reduced RUNX1 level, which was upregulated in COAD and its high level predicted poor prognosis. RIPK4 is positively associated with RUNX1 in COAD. Overexpressing RUNX1 antagonized the suppression of RIPK4 knockdown on RUNX1, Wnt3a, p-GSK-3β, cytoplasmic β-catenin, nuclear β-catenin, Cyclin D1, CDK4, Cyclin E, and c-Myc levels. Collectively, miR-575/RIPK4 axis repressed COAD progression via inactivating the Wnt/β-catenin pathway through downregulating RUNX1.
研究领域:
肿瘤学
·
分子生物学
·
生物信息学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR CARCINOGENESIS
·
2023
·
IF 4.6
Miao Deng,Jiaxin Guo,Zihang Ling,Chi Zhang,Lihong He,Zhaona Fan,Bin Cheng,Juan Xia
Gene mutations play an important role in head and neck squamous cell carcinoma (HNSCC) by not only promoting the occurrence and progression of HNSCC but also affecting sensitivity to treatment and prognosis. KRAS is one of the most frequently mutated oncogenes, which has been reported to have a mutation rate from 1.7% to 12.7% and may lead to poor prognosis in HNSCC, but its role remains unclear. Here, we found that the KRAS mutation can promote HNSCC generation through synergism with 4-Nitroquinoline-1-Oxide(4NQO). Mechanistically, KRAS mutations can significantly upregulate Runx1 to promote oral epithelial cell proliferation and migration and inhibit apoptosis. Runx1 inhibitor Ro 5-3335 can effectively inhibit KRAS -mutated HNSCC progression both in vitro and in vivo. These findings suggest that the KRAS mutation plays an important role in HNSCC and that Runx1 may be a novel therapeutic target for KRAS -mutated HNSCC.
研究领域:
肿瘤学
·
分子生物学
·
癌症遗传学
✓ 已验证
DOI
PubMed
高影响因子
DEVELOPMENT
·
2024
·
IF 3.7
Yu Meng,Thorner Konrad,Parameswaran Sreeja,Wei Wei,Yu Chuyue,Lin Xinhua,Kopan Raphael,Hass Matthew R.
The conserved Runt-related (RUNX) transcription factor family are master regulators of developmental and regenerative processes. Runx1 and Runx2 are expressed in satellite cells (SC) and in skeletal myotubes. Conditional deletion of Runx1 in adult SC negatively impacted self-renewal and impaired skeletal muscle maintenance even though Runx2 expression persisted. Runx1 deletion in C2C12 cells that retain Runx2 expression identified unique molecular functions of Runx1 that cannot be compensated by Runx2. The reduced myoblast fusion in vitro caused by Runx1 loss was due in part to ectopic expression of Mef2c, a target repressed by Runx1 . Structure-function analysis demonstrated that the Ets-interacting MID/EID region of Runx1, absent from Runx2, is critical to Runx1 myoblast function and for Etv4 binding. Analysis of ChIP-seq datasets from Runx1 (T-cells, muscle) versus Runx2 (preosteoblasts) dependent tissues identified a composite Ets:Runx motif enriched in Runx1 -dependent tissues. The Ets:Runx composite motif was enriched in peaks open exclusively in ATAC-seq datasets from WT cells compared to ATAC peaks unique to Runx1KO cells. Thus, engagement of a set of targets by the RUNX1/ETS complex define the non-redundant functions of Runx1 .
研究领域:
分子生物学
·
细胞生物学
·
转录因子
·
肌肉再生
✓ 已验证
DOI
高影响因子
Journal of Environmental Sciences
·
2024
·
IF 5.9
Long Zhu,Shangjie Zhou,Li Huang,Xiaotian Wang,Yutong Huang,Jiachen Yu,Zaizhao Wang
Bisphenol A (BPA) is a recognized estrogenic endocrine disruptor that poses a threat to the reproductive health of fish. However, it remains unclear whether and how paternal BPA exposure can lead to developmental toxicity in offspring. To explore the potential paternal BPA exposure impacts on craniofacial cartilage growth in offspring, male rare minnows were subjected to BPA and subsequently mated with normal females to produce progeny. Our results demonstrated that paternal BPA exposure resulted in increased malformation and delayed craniofacial cartilage development in the F1 offspring. Furthermore, BPA exposure led to differential expression of 28 miRNAs in paternal sperm in F0 generation (13 upregulated and 15 downregulated), among which 7 miRNAs were involved in the regulation of bone development. BPA also downregulated the expression of bmp2a and Runx1 during F1 embryonic development. The inhibited bmp2a expression might derive from BPA's stimulation of one miRNA, aca-miR-16a-5P, due to bmp2a being one of its target genes. Notably, paternal BPA exposure did not affect craniofacial cartilage development or gonadal development in the F2 generation. Overall, our study sheds light on the molecular mechanisms underlying the impact of paternal BPA exposure on facial chondrogenesis in offspring and provides theoretical support for the ecological protection of fish populations.
研究领域:
环境毒理学
·
发育生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2019
·
IF 1.984
Liwen Han,Haotian Kong,Fasheng Liu,Xiaobin Li,Shanshan Zhang,Xuanming Zhang,Yong Wu,Hua Yang,Aiping Zhang,Kechun Liu
The aim of the study is to explore the protective effect of new gelatin (NG, Xin’ejiao in China) on hematopoietic injury caused by chemotherapy. Zebrafish, at 48 hours post fertilization (hpf), was treated with different chemotherapeutic drugs to establish the zebrafish hematopoietic damage model with reduced thrombocytes and erythrocytes. The protecting effects of NG on the thrombocytes and erythrocytes were observed, respectively, on zebrafish models. Then, the RT-PCR method was used to detect the change of mRNA level of the hematopoiesis-related cytokines scl1, c-myb, pu.1, GATA1, and runx1 genes. The results showed that 50 μg·mL−1 and 100 μg·mL−1 NG rescued and increased the thrombocytes numbers induced by vinorelbine (NVB) and chloramphenicol (CHL) and the erythrocytes numbers induced by methotrexate (MTX), doxorubicin (ADM), and mechlorethamine hydrochloride (MH) in zebrafish models. Meanwhile, the mRNA expression of scl1, c-myb, and GATA1 genes in the NG treatment group was raised compared with the MTX treatment group. Also, the mRNA expression of pu.1 and Runx1 in the NG treatment group was reduced compared with the MTX treatment group. In consequence, traditional Chinese medicine NG showed a certain degree protective effect on hematopoiesis injury induced by chemotherapy in this study, which may depend on the promotion of erythrocytes proliferation and the regulation of the hematopoietic genes level.
研究领域:
药理学
·
血液学
·
分子生物学
·
斑马鱼研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Biological Sciences
·
2026
·Vol. 22
·期 4
·1775-1792
·
IF 10
Shen Siman,Ying Chen,Fu Xinglin,Zeng Xiaobian,Guo Xiuli,Wu Han,Zhang Liangqing,Xu Li
Background: Persistently elevated glycolysis is increasingly recognized as a driving force in diabetic kidney disease (DKD). As a product of glycolysis, lactate can induce histone lactylation, an emerging epigenetic mechanism associated with post-transcriptional modification. However, the molecular mechanism and clinical impact of histone lactylation in DKD remain largely understood.Methods and Results: Spatial transcriptomics analysis revealed upregulation of glycolytic genes in tubular epithelial cells (TECs), thus leading to elevated levels of renal lactate accumulation. PKM2 deficiency lowered the lactate production during the fibrotic process and decreased histone lactylation. Mechanistically, ChIP-seq & RNA-seq results showed lactate promoted histone H4 lysine 12 lactylation (H4K12la), which in turn enhanced RUNX1 transcription. RUNX1 subsequently activated HK1 and SLC2A1, which accelerated glycolysis and renal fibrosis of DKD. Further, SIRT3 expression was significantly decreased in the renal tubular cells in DKD. Furthermore, insufficient SIRT3 is functionally promote renal fibrosis by directly deacetylating RUNX1 at H4K12, leading to attenuated glycolytic process, and subsequently robust glycolytic ability and increased production of lactate.Conclusion: Thus, the study links RUNX1-mediated glycolysis to SIRT3-mediated histonelactylation epigenetic reprogramming in promoting the fibrotic process, providing better understanding of epigenetic regulation of DKD pathogenesis, and new therapeutic strategy for DKD.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
·
2022
·Vol. 36
·期 4
·e22994
·
IF 3.568
Mingxin Liu,Guizhou Tao,Yiming Cao,Yu Hu,Zhe Zhang
Atherosclerosis (AS) is a chronic inflammatory disease with the formation and accumulation of macrophage-derived foam cells in the subendothelial space of blood vessels as one major characteristic. Insulin-like growth factor 2 messenger RNA (mRNA) binding protein 1 (IGF2BP1) is an RNA-binding factor and its elevation has been reported to be associated with macrophage infiltration into the atherosclerotic vascular wall. This study aims to investigate the roles of IGF2BP1 in AS-associated foam cell formation. Herein, ApoE−/− mice fed with high-fat diet developed atherosclerotic lesions in the aorta, where IGF2BP1 expression was upregulated and autophagy was impaired. IGF2BP1 expressed in F4/80+ macrophages and coexisted with p62. In vitro, IGF2BP1 expression was upregulated in RAW264.7 macrophages exposed to oxidized low-density lipoprotein (ox-LDL) (100 μg/ml). Interestingly, silencing of IGF2BP1 ameliorated ox-LDL-induced lipid accumulation and inflammation, and enhanced autophagic flux in macrophages. Furthermore, the expression of RUNX family transcription factor 1 (RUNX1), a gene that is able to inhibit autophagy in multiple cell types, was elevated in atherosclerotic aortas and in ox-LDL-treated macrophages. In addition, RNA immunoprecipitation results revealed that IGF2BP1 is bound to RUNX1 mRNA. Alterations induced by IGF2BP1 knockdown in ox-LDL-treated macrophages were abolished by RUNX1 overexpression. Furthermore, after autophagy inhibitor 3-methyladenine administration, silencing of IGF2BP1-reduced lipid accumulation and inflammation were recovered in RAW264.7 cells. In summary, our study demonstrated that silencing of IGF2BP1 restrained ox-LDL-induced lipid accumulation and inflammation by reducing RUNX1 expression and facilitating autophagy in macrophages. IGF2BP1/RUNX1 axis may be considered as a potential therapeutic target in AS.
研究领域:
心血管疾病
·
分子生物学
·
免疫学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Communications Biology
·
2025
·
IF 5.1
Wang Shanshan,Wu Zankai,Song Wenqin,Zhang Hui,Bu Xueshan,Gao Wenwei,Wu Kefan,Xia Zhongyuan,Zhao Bo,Wang Wei
Activation of the cGAS-STING pathway has been proposed as a potential pathogenic mechanism underlying postoperative cognitive dysfuncton (POCD). Analysis of public transcriptomic data from the hippocampus of male mice suggests upregulation of Rbm47 in an experimental POCD model. In vitro, knockdown (KD) of Rbm47 in BV2 cells reduces levels of cGAS, STING, TNF-α, IL-6, and IFN-β under isoflurane and lipopolysaccharide (Iso + LPS) conditions. HT22 cells exposed to culture medium from Rbm47 -KD BV2 cells treated with Iso + LPS show increased levels of MEF2C, GPX4, GSH, and SOD, and reduced levels of MDA and iron. Microglial Rbm47 overexpression amplifies cGAS-STING signaling and aggravates neuronal ferroptosis, which is reversed by the cGAS inhibitor RU.521. Rbm47 KD combined with RU.521 treatment synergistically ameliorates POCD in male mice. Mechanistically, the RRM2 domain of RBM47 interacts with the 3’UTR of cGAS mRNA, enhancing its stability. RUNX1 directly binds to the Rbm47 promoter and facilitates its transcription. RUNX1 overexpression activates the RBM47-cGAS-STING axis and exacerbates neuronal ferroptosis. Conversely, RUNX1 ablation ameliorates POCD, dampens the cGAS-STING signaling, and inhibits ferroptosis, which is abolished by RBM47 depletion. Our findings suggest that repression of RUNX1/RBM47 may represent a promising therapeutic strategy for POCD.
研究领域:
神经科学
·
分子生物学
·
免疫学
·
细胞生物学
·
麻醉与围术期医学
✓ 已验证
DOI
PubMed
高影响因子
Genes
·
2020
·Vol. 11
·期 5
·495
·
IF 3.759
Yuyi Zhong,Liying Li,Yingting He,Bo He,Zhonghui Li,Zhe Zhang,Hao Zhang,Xiaolong Yuan,Jiaqi Li
H3K27me3 is an epigenetic modification that results in the repression of gene transcription. The transcription factor RUNX1 (the runt-related transcription factor 1) influences granulosa cells’ growth and ovulation. This research uses ELISA, flow cytometry, EDU, ChIP-PCR, WB and qPCR to investigate steroidogenesis, cell apoptosis, and the proliferation effect ofRUNX1in porcine granulosa cells (pGCs) as regulated by H3K27me3. Decreased H3K27me3 stimulates the expression of steroidogenesis-related genes, includingCYP11A1,PTGS2, andSTAR, as well as prostaglandin. H3K27me3 transcriptionally repressesRUNX1here, whereas RUNX1 acts as an activator ofFSHR,CYP11A1, andCYP19A1, promoting the production of androgen, estrogen, and prostaglandin, as well as increasing anti-apoptotic and cell proliferation activity, but decreasing progesterone. Both the complementary recovery of the H3K27me3 antagonist with the siRUNX1 signal, and the H3K27me3 agonist with the RUNX1 signal to maintain RUNX1 lead to the activation ofCYP19A1,ER1,HSD17β4, andSTARhere. Androgen and prostaglandin are significantly repressed but progesterone is markedly increased with the antagonist and siRUNX1. Prostaglandin is significantly promoted with the agonist and RUNX1. Furthermore, H3K27me3-RUNX1 affects the anti-apoptotic activity and stimulation of proliferation in pGCs. The present work verifies the transcriptional suppression ofRUNX1by H3K27me3 during antral follicular development and maturation, which determines the levels of hormone synthesis and cell apoptosis and proliferation in the pGC microenvironment.Keywords:H3K27me3;RUNX1;granulosa cells;steroidogenesis;cell apoptosis and proliferation;antral follicles;pigs
研究领域:
分子生物学
·
生殖生物学
·
表观遗传学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）