Frontiers in Pharmacology
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2018
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IF 3.831
Zhang Zhi-Hao,Li Ming-Hua,Liu Dan,Chen Hua,Chen Dan-Qian,Tan Ning-Hua,Ma Shuang-Cheng,Zhao Ying-Yong
Tubulointerstitial fibrosis is the final common pathway for all kidney diseases leading to chronic kidney disease (CKD). TGF-β/Smad signaling pathway plays a key role in renal fibrosis. Previous studies have revealed that rhubarb extracts attenuated the increase of transforming growth factor-β 1 (TGF-β1) in CKD rats. To gain an in-depth insight into the mechanism of the anti-fibrotic activities of the rhubarb extracts, we investigated the influence of rhubarb extracts on TGF-β/Smad signaling pathway and the influence on metabolome in a rat model of CKD with adenine-induced chronic tubulointerstitial nephropathy. Male Sprague-Dawley rats were divided into four groups, including control, CKD, CKD + petroleum ether extract, CKD + ethyl acetate extract, and CKD + n-butanol extract groups. Kidneys harvested on the week three were evaluated for renal fibrosis, the expression of proteins in TGF-β/Smad signaling pathway and metabolomic study. We found rhubarb extracts suppressed TGF-β/Smad3-mediated renal fibrosis by reducing the TGF-β1, transforming growth factor-β receptor I (TGF-β RI), transforming growth factor-β receptor II (TGF-β RII), Smad2, p-Smad2, Smad3, p-Smad3, and Smad4, meanwhile increased Smad7. In addition, rhubarb extracts mitigated renal injury and dysfunction, and either fully or partially reversed the abnormalities of tissue metabolites. Thus, rebalancing the disorder of TGF-β/Smad signaling and metabolic dysfunction by treatment with rhubarb extracts may represent as an effective therapy for CKD associated with fibrosis.
研究领域:
药理学
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肾病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2023
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IF 14
Hong-Lin Qian,Sheng-Yu Chen,Fan Jia,Wei-Pin Huang,Jing Wang,Ke-Feng Ren,Guo-Sheng Fu,Jian Ji
The valid management of inflammation and precise inhibition of smooth muscle cells (SMCs) is regarded as a promising strategy for regulating vascular responses after stent implantation , yet posing huge challenges to current coating constructions. Herein, we proposed a spongy cardiovascular stent for the protective delivery of 4-octyl itaconate (OI) based on a “spongy skin” approach, and revealed the dual-regulation effects of OI for improving vascular remolding. We first constructed a “spongy skin” onto poly-l-lactic acid (PLLA) substrates, and realized the protective loading of OI with the highest dosage of 47.9 μg/cm 2 . Then, we verified the remarkable inflammation mediation of OI, and surprisingly revealed that the OI incorporation specifically inhibited SMC proliferation and phenotype switching, which contributed to the competitive growth of endothelial cells (EC/SMC ratio ∼ 5.1). We further demonstrated that OI at a concentration of 25 μg/mL showed significant suppression of the TGF-β/Smad pathway of SMCs, leading to the promotion of contractile phenotype and reduction of extracellular matrix. In vivo evaluation indicated that the successful delivery of OI fulfilled the inflammation regulation and SMCs inhibition, therefore suppressing the in-stent restenosis. This “spongy skin” based OI eluting system may serve as a new strategy for improving vascular remolding, and provides a potential concept for the treatment of cardiovascular diseases.
研究领域:
心血管工程
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生物材料
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药物递送系统
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血管生物学
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组织工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR PHYSIOLOGY
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2018
·Vol. 234
·期 3
·2537-2551
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IF 3.923
Hai-Ming Xu,Feng-Hua Sui,Mei-Hua Sun,Gong-Liang Guo
Recent studies have shown that circulating microRNAs (miRNA) play a critical role in diagnosing acute coronary syndrome (ACS). This study aims to investigate the effect of miR-224 on atherosclerotic plaques forming and vascular remodeling in ACS and its relationship with TGF-β/Smad pathway. Myocardial infarction (MI) rat model was established and lentivirus vector of miR-224 inhibitor was prepared for investigating the effect of downregulated miR-224 on the contents of nitric oxide (NO) and endothelin-1 (ET-1), blood lipid levels and inflammatory factor levels in serum as well as the TGF-β/Smad pathway. The rats suffering from MI had decreased survival rates and exhibited reduced levels of NO, high-density lipoprotein cholesterol, and lumen diameter, and Smad7 messenger RNA (mRNA) and protein expression; while had significantly increased ratio of heart weight or body weight, levels of ET-1, inflammatory factors, blood lipid indexes, vascular remodeling indexes, collagen volume fraction, vulnerable atherosclerotic plaque area, VCAM-1 and MMP-2 protein expression, TGF-β, Smad2, Smad3, and Smad4 mRNA and protein expression. After inhibiting the TGF-β/Smad pathway, the rats suffering from MI showed notably opposite trend. In conclusion, downregulation of miR-224 expression promotes the formation of vulnerable atherosclerotic plaques and vascular remodeling in ACS through activation of the TGF-β/Smad pathway. Therefore, this study provides a new therapeutic target for ACS.
研究领域:
心脏病学
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分子生物学
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病理生理学
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产品关联
DOI
PubMed
高影响因子
HISTOCHEMISTRY AND CELL BIOLOGY
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2023
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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
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2024
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IF 4.4
Feng Sa,Liu Linyan,Cheng Yuelin,Zhou Mengmeng,Zhu Haoqiang,Zhao Xinyan,Chen Ziyu,Kan Shunli,Fu Xuanhao,Hu Wei,Zhu Rusen
Objective: The limited ability to regenerate axons after spinal cord injury (SCI) is influenced by factors such as astrocyte activation, reactive proliferation, and glial scar formation. The TGF-β/Smad (transforming growth factor-β/mothers against decapentaplegic homolog) pathway, associated with astrocytic scarring, plays a crucial role in recovery post-injury. This study aims to investigate how icariin (ICA) interacts with reactive astrocytes in the treatment of spinal cord injury.Methods: A rat SCI model was constructed, and the recovery of motor function was observed after treatment with ICA.HE staining, LFB staining, immunofluorescence staining, and Western blotting were employed to assess ICA's ability to inhibit astrocyte proliferation in rats following spinal cord injury by modulating YAP, as well as to evaluate the reparative effects of ICA on the injured spinal cord tissue. Primary astrocytes were isolated and cultured. Immunoprecipitation-Western Blot (IP-WB) ubiquitination and cytoplasm-nuclear separation were employed to assess PPM1B ubiquitination and nuclear translocation.Results: The CatWalk XT gait analysis, BBB (Basso, Beattie, and Bresnahan) score, electrophysiological measurements, HE staining, and LFB staining collectively demonstrated that ICA promotes motor function and tissue recovery following spinal cord injury in rats. Immunofluorescence staining and Western Blot analyses revealed that ICA inhibits astrocyte proliferation in rats post-spinal cord injury by suppressing YAP activity. Furthermore, the activation of YAP by XMU-MP-1 was shown to compromise the efficacy of ICA in these rats after spinal cord injury. Additional immunofluorescence staining and Western Blot experiments confirmed that ICA inhibits TGFβ1-induced astrocyte activation through the regulation of YAP. The knockdown of PPM1B (protein phosphatase, Mg2+/Mn2+-dependent 1B) in astrocytes was found to inhibit TGFβ signaling. Additionally, YAP was shown to regulate PPM1B ubiquitination and nuclear translocation through immunoprecipitation-Western blot analysis, along with the segregation of cytoplasm and nucleus.Conclusion: Icariin promotes functional recovery in rats after spinal cord injury by inhibiting YAP and regulating PPM1B ubiquitination to inhibiting the activation of reactive astrocytes.
研究领域:
神经科学
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Advanced Fiber Materials
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2025
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IF 21.3
Li Chao,Li Wentao,Deng Ronghui,Huang Lingan,Song Yifan,Wei Xianjie,Xu Bingbing,Cui Guoqing,Chen Zehao,Yu Jiakuo
Excessive interface friction and advanced glycation end products (AGEs) disrupt collagen ordered deposition, promoting scar formation in tendinopathies. Inspired by tendon sheath anatomy, we developed a bionic bilayer nano-membrane via electrospinning and photocrosslinking to initiate the directional and orderly regeneration process of tendon tissue. The lubricating layer (PP), containing phosphatidylserine (PS), reduces frictional stress, while the regenerative layer (GM/GV), composed of gelatin methacrylate (GM) and vanillin-modified gelatin (GV), scavenges ROS and mitigates AGEs-induced collagen disorder deposition. This parallel bilayer structure guides tendon cell alignment and promotes ordered collagen deposition. Additionally, vanillin suppresses the AGEs/TGF-β/Smad pathway, reducing scar formation and tissue adhesion. In vitro/in vivo tests showed a fivefold decrease in coefficient of friction (COF) and a tenfold increase in Achilles tendon function index (AFI) compared to the PCL and normal groups, respectively. The PP@GM/GV membrane, regulated by mechano-biochemical coupling factors, offers a promising strategy for tendinopathy repair, and holds significant potential for clinical translation in guiding functional tendon regeneration and improving patient outcomes. Graphical
研究领域:
生物医学工程
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组织工程
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再生医学
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生物材料
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骨科
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产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
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2024
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IF 8.3
Qiuhui Hu,Yongzhao Su,Siying Ma,Peiying Wei,Chengbin He,Di Yang,Yue Qian,Youqing Shen,Xiaoxuan Zhou,Zhuxian Zhou,Hongjie Hu
Liver fibrosis is the critical stage in the development of chronic liver disease (CLD), from simple injury to irreversible cirrhosis. Timely detection and intervention of liver fibrosis are crucial for preventing CLD from progressing into a fatal condition. Herein, we developed iron oxide (Fe3O4) nanoparticles (IONPs) and ferulic acid (FA) coencapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), followed by surface modification with cRGD peptides (cRGD-PLGA/IOFA) for integrin-targeted clinical magnetic resonance imaging (MRI)-traceable treatment of liver fibrosis. The cRGD peptide linked on the surface of the PLGA/IOFA NPs could specifically bind to the overexpressed integrin αvβ3 on activated hepatic stellate cells (HSCs) in the fibrotic liver, enabling the high-sensitive clinical MR imaging (3 T) and precise staging of liver fibrosis. The FA encapsulated in cRGD-PLGA/IOFA showed excellent efficacy in reducing oxidative stress and inhibiting the activation of HSCs through the transforming growth factor-β (TGF-β)/Smad pathway. Notably, the IONPs encapsulated in cRGD-PLGA/IOFA NPs could alleviate liver fibrosis by regulating hepatic macrophages through the NF-κB pathway, lowering the proportion of Ly6Chigh/CD86+, and degrading collagen fibers. The FA and IONPs in the cRGD-PLGA/IOFA produced a synergistic enhancement effect on collagen degradation, which was more effective than the IONPs treatment alone. This study demonstrates that cRGD-PLGA/IOFA NPs could effectively relieve liver fibrosis by acting on macrophages and HSCs and provide a new strategy for the clinical MRI-traceable treatment of liver fibrosis.
研究领域:
纳米技术
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生物医学工程
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药理学
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医学影像
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肝病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）