Journal of Cardiovascular Translational Research
·
2025
·
IF 2.5
Hou Xiaolu,Hu Guoling,Wang Heling,Yang Ying,Sun Qi,Bai Xiuping
Heart failure (HF) is a clinical syndrome caused by structural or functional abnormalities in heart. Egr2 has been reported to be protective for multiple diseases, but its effect on HF remains unknown. The present study intended to investigate the potential role of Egr2 in HF and its possible downstream effectors. High Egr2 expression in heart was observed in HF mice. Egr2 knockdown alleviated cardiac damage and function in HF mice. Egr2 knockdown inhibited myocardial inflammation and apoptosis both in vivo and in vitro. Egr2 inhibited Acot1 transcription expression via directly binding to its promoter. Acot1 overexpression reduced Lipopolysaccharide (LPS)-induced cardiomyocyte inflammation and apoptosis. Functional rescue experiments revealed that Acot1 reversed the effects of Egr2 on LPS-induced cell apoptosis and inflammation. Overall, Egr2 knockdown might ameliorate HF by inhibiting inflammation and apoptosis in cardiomyocytes by targeting Acot1. This study might provide evidence to better understand the molecular mechanisms of HF pathogenesis. Graphical Egr2 knockdown might ameliorate HF by inhibiting inflammation and apoptosis in cardiomyocytes, possibly through Acot1.
研究领域:
心血管生物学
·
分子医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Zheng Wang,Mingyu Zhao,Yue Su,Qiangsen Zhao,Zhenhua Ma,Qiaoxian Yue,Zhiwei Zhu,Lihuan Zhang,Zhuocheng Hou,Huifeng Li
Excessive abdominal fat deposition negatively impacts poultry meat production and carcass yield. Identification of novel adipogenesis regulators may help improve production performance declines caused by excessive fat deposition. NUMB Endocytic Adaptor Protein ( NUMB ) typically functions as a cell fate determinant and plays a significant role in cell development and various diseases. Here, we found that NUMB is abundantly expressed in chicken abdominal fat depots and is induced in cultured adipocytes following adipogenic treatment. The gain- and loss-of-function experiments demonstrated that NUMB promotes the proliferation and G1/S transition of chicken adipocytes, enhances adipocyte differentiation, and increases the expression of PPARγ1 transcript. Through mRNA-seq analysis and molecular experiments, we further confirmed that NUMB inhibits the transcriptional activation of the NOTCH1 pathway and the expression of the downstream transcription factor HES1 by inducing NOTCH1 degradation. Nevertheless, the inhibition of the NOTCH1 / HES1 axis alone cannot fully explain NUMB 's role in adipogenesis, as NUMB also regulates the expression of multiple adipogenic transcription factors such as E2F1 , EGR2 , and NR4A3 . Our data suggest that NUMB is a potent activator of adipogenesis and enhances our understanding of its regulatory mechanisms in chicken abdominal fat deposition.
研究领域:
动物科学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Zhixiang Mu,Tianxi Shen,Hui Deng,Bairui Zeng,Chen Huang,Zhengjin Mao,Yuyu Xie,Yu Pei,Liting Guo,Rongdang Hu,Limin Chen,Yunlong Zhou
Modulating the properties of biomaterials in terms of the host immune response is critical for tissue repair and regeneration. However, it is unclear how the preference for the cellular microenvironment manipulates the chiral immune responses under physiological or pathological conditions. Here, we reported that in vivo and in vitro oligopeptide immunosuppressive modulation was achieved by manipulation of macrophage polarization using chiral tetrapeptide (Ac-FFFK-OH, marked as FFFK) supramolecular polymers. The results suggested that chiral FFFK nanofibers can serve as a defense mechanism in the restoration of tissue homeostasis by upregulating macrophage M2 polarization via the Src-STAT6 axis. More importantly, transiently acting STAT6, insufficient to induce a sustained polarization program, then passes the baton to EGR2, thereby continuously maintaining the M2 polarization program. It is worth noting that the L-chirality exhibits a more potent effect in inducing macrophage M2 polarization than does the D-chirality, leading to enhanced tissue reconstruction. These findings elucidate the crucial molecular signals that mediate chirality-dependent supramolecular immunosuppression in damaged tissues while also providing an effective chiral supramolecular strategy for regulating macrophage M2 polarization and promoting tissue injury repair based on the self-assembling chiral peptide design.
研究领域:
生物材料
·
免疫学
·
组织工程
·
分子生物学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
HISTOCHEMISTRY AND CELL BIOLOGY
·
2023
·
IF 2.3
Jin Xin,Xu Hainan,Hu Qing,Yin Yitong,Qin Meiying,Xia Zhijun
Pelvic organ prolapse (POP) is a common disorder among women that negatively affects women’s quality of life. Early growth response 2 (EGR2) is a transcription factor that regulates cell growth. The present study aimed to explore the role of EGR2 in POP progression and provided a new target for the treatment and prevention of POP. Firstly, we extracted primary vaginal anterior wall fibroblasts from POP tissues and non-POP tissues and then constructed an EGR2-silencing lentivirus for further study. Immunoblotting, qPCR, TUNEL assay, CCK-8 assay, dual luciferase assay, and ELISA assay were carried out. EGR2 expression was much higher in POP tissues than in control tissues, and EGR2 expression positively correlated with cytokine signaling 3 (SOCS3) expression. Knockdown of EGR2 increased cell proliferation, upregulated PCNA expression, and reduced apoptosis in POP fibroblasts. Moreover, we found that the knockdown of EGR2 increased COL1A1 , COL3A1 , and Elastin expression and decreased MMP2 and MMP9 activities, and knockdown of EGR2 increased TGF-β/Smad pathway activity in POP fibroblasts. Interestingly, the results of dual luciferase assay demonstrated that EGR2 was able to increase SOCS3 transcriptional activity. EGR2 knockdown alleviated the apoptosis of POP fibroblasts by reducing SOCS3 expression and improving the proliferation and collagen synthesis of POP fibroblasts. Overall, our study illustrated that EGR2 was highly expressed in POP tissues, and knockdown of EGR2 alleviated apoptosis and reduced matrix degradation in POP fibroblasts. This study might provide a new insight into the pathogenesis of POP.
研究领域:
妇科学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AMERICAN JOURNAL OF SPORTS MEDICINE
·
2025
·
IF 4.5
Baoyun Xu,Yunjiao Wang,Gang He,Xu Tao,Shang Gao,Mei Zhou,Yuzhen Tang,Kang-lai Tang,Lin Guo,Wan Chen
Background:The challenge of achieving effective tendon-to-bone healing remains a significant concern in sports medicine, necessitating further exploration. Biomimetic electrospun nanomaterials present promising avenues for improving this critical healing process.Purpose:To investigate the biological efficacy of a novel aligned-to-random PLGA/Col1-PLGA/nHA bilayer electrospun nanofiber membrane in facilitating tendon-to-bone healing.Study Design:Controlled laboratory study.Methods:The bilayer membrane’s composition, combining PLGA/Col1 for tendon attachment and PLGA/nHA for bone integration, was examined using scanning electron microscopy, Fourier transform infrared spectroscopy, and mechanical testing. Positioned between the Achilles tendon and bone, its design aimed for harmonious integration with both types of tissue. In vitro, biocompatibility, cell adhesion, and proliferation of the biomaterial were evaluated using live/dead staining and the CCK-8 assay. Collagen secretion and mineralization were measured for 2 cell types. In vivo, tendon-to-bone insertion samples harvested from mice were analyzed: micro–computed tomography assessed bone formation; histological staining evaluated chondrogenesis, tendinogenesis, and the 4-layer structure of the insertion; and biomechanical testing measured insertion strength. Real-time polymerase chain reaction identified genes involved in tendon-to-bone healing, and transcriptome analysis elucidated the underlying cellular and molecular mechanisms.Results:The optimal composition was determined as 10% 3:1 for aligned PLGA/Col1 and 9% 5:1 for PLGA/nHA. Coculture showed minimal cell death, firm cell adherence, and steady proliferation, with PLGA/Col1 enhancing collagen secretion. In vivo, the material promoted bone and cartilage formation and improved tendon-to-bone interface strength. Transcriptome analysis indicated links to TNF and NF-κB pathways and to genes IL-1β, ADAM8, and EGR2.Conclusion:The novel aligned-to-random PLGA/Col1-PLGA/nHA bilayer nanofiber membrane outperformed other materials in both in vitro and in vivo evaluations, significantly enhancing tendon-to-bone healing. It notably improved cartilage and bone formation, tendon maturation, and biomechanical strength at the surgical interface. These effects may be associated with the TNF and NF-κB pathways and with the genes IL-1β, ADAM8, and EGR2.Clinical Relevance:This study introduces a biomimetic nanofiber membrane enhancing tendon-to-bone healing, which is crucial for sports medicine. Its efficacy in improving healing outcomes, including bone and cartilage formation and biomechanical strength, could significantly lower failure rates in surgical procedures such as rotator cuff repair and anterior cruciate ligament reconstruction. This advancement offers promising implications for patient recovery and the effectiveness of surgical interventions in tendon-to-bone injuries.
研究领域:
运动医学
·
组织工程
·
生物材料科学
·
骨科
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）