CELLULAR AND MOLECULAR BIOLOGY
·
2023
·Vol. 69
·期 9
·
IF 1.6
Aili Xuan,Mei Yang,Qun Xia,Qian Sun
Asthma is a respiratory inflammatory disease, and nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) is involved in the progression of respiratory diseases. However, the role of NOX4 in asthma remains unclear. In the present study, we aimed to explore the effects of NOX4 on airway remodeling and inflammation. NOX4 expression was measured using immunocytochemistry (IHC), western blot, and real-time PCR (qPCR). Lung tissues were stained using the H&E assay. ELISA was used to examine the levels of airway remodeling-related indicators, and qPCR was used to detect airway inflammatory factors. The results indicated that NOX4 is highly expressed in lung tissues, bronchoalveolar lavage fluid (BALF), and serum of OVA-treated mice. Inhibition of NOX4 alleviated OVA-induced airway remodeling and inflammation. Similarly, TGF-β1 was also upregulated in BALF and serum OVA-induced mice. Inhibition of TGF-β1 signaling also improved airway remodeling and inflammation induced by OVA. Moreover, the downregulation of NOX4 inactivated the TGF-β1-Smad2/3 pathway, and TGF-β1 decreased Smad2/3 expression. Moreover, inhibition of the TGF-β1 was enhanced, while TGF-β1 reversed the effects on airway remodeling and inflammation induced by NOX4 inhibition. Taken together, the downregulation of NOX4 improves airway remodeling and inflammation via inactivation of the TGF-β1-Smad2/3 pathway in asthma mice, suggesting that NOX4 may be a therapeutic target for asthma.
研究领域:
呼吸系统疾病
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分子生物学
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免疫学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Xu Dong,Jianyin Miao,Ling Wu,Ziyu Kong,Zenghui Liu,Diyi Jia,Qingqing Zhai,Dan Zhang,Yan Xu
Background Diabetes patients face an elevated wound infection susceptibility and delayed healing processes. Currently, no existing literature has reported on the effect and mechanism of theaflavin-3, 3’-digallate nanoparticles (TFDG NPS) and TFDG NPS@hydrogels on diabetic wounds. Purpose Given that the treatment options for diabetic wound are limited, the aim of this study is to develop an innovative therapeutic approach to address diabetic wounds. Methods The TFDG NPS were prepared using ionic cross-linking, and they were then characterized. The biocompatibility of the TFDG NPS and TFDG NPS@hydrogel was assessed using a Cell Counting Kit-8 (CCK-8) assay and live/dead staining on HK-2 cells in vitro . Diabetic ICR mice were induced through intraperitoneal injection of streptozocin (STZ). They were then subjected to the creation of two full-thickness wounds on their dorsal areas. The effect and mechanism of the TFDG NPS and TFDG NPS@hydrogel on wound healing in diabetic mice were evaluated using a histological analysis, a western blot analysis, and molecular docking. Results The optimal TFDG NPS proportion was found to be TFDG:Gelatin (Gel):Chitosan (CS) = 2:1:1. Images photographed using a transmission electron microscope (TEM) revealed that the TFDG NPS appeared spherical, with a diameter of approximately 140 ± 20 nm. The favorable bio-compatibility of the TFDG NPS and TFDG NPS@hydrogel was confirmed using cell experiments. Animal studies demonstrated that both the TFDG NPS and TFDG NPS@hydrogel enhanced collagen fiber accumulation and new blood vessel density, reduced F4/80 infiltration, and upregulated the expression levels of TGF-β1, SMAD3, Collagen I, and α-SMA. The potential mechanism may involve activation of the TGF-β1/SMAD3 pathway, stimulating the secretion of Collagen I and α-SMA, and thereby facilitating wound closure in diabetic mice. The molecular docking results confirmed a high affinity between TFDG and TGF-β1/SMAD3. Conclusion TFDG NPS and TFDG NPS@hydrogel promoted wound closure in diabetic mice through the TFG-β1/SMAD3 pathway, thus exhibiting promising therapeutic potential for diabetic wound treatment.
研究领域:
医学
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生物材料学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICAL RESEARCH
·
2023
·Vol. 28
·期 1
·1-12
·
IF 4.2
Jia Ji,Zhao Xing-an,Tao Si-ming,Wang Jun-wen,Zhang Rong-liang,Dai Hua-lei,Zhang Xin-jin,Han Ming-hua,Yang Bei,Li Yu,Li Jin-tao
Background Postinfarction cardiac remodeling presents a compensatory mechanism aimed at mitigating congestive heart failure. It is distinguished by progressive dilatation and hypertrophy of the ventricular chambers, fibrotic alterations, and prolonged apoptosis of cardiomyocytes. The primary objective of this study was to assess the effects of icariin on myocardial fibrosis and ventricular remodeling in rats subjected to myocardial infarction (MI).Methods Male Sprague‒Dawley (SD) rats were subjected to randomization and subsequently divided into distinct groups: the control group, the sham group (undergoing sham operation), the MI group (experiencing ligation of the left anterior descending artery), and the icariin group. Within the icariin group, rats were further categorized into three different dose groups based on the administered icariin dosage: the MI30 group (30 mg/kg/day), the MI60 group (60 mg/kg/day), and the MI120 group (120 mg/kg/day). Cardiac function evaluation was carried out using echocardiography. Histological examinations, including hematoxylin and eosin (HE) staining, Masson staining, and immunohistochemistry studies, were conducted 90 days after the occurrence of MI. Additionally, Western blotting was employed to assess TGF‐β1, p-Smad2, and p-Smad3 levels.Results The administration of icariin revealed a noteworthy enhancement in cardiac function among rats afflicted with left anterior descending coronary artery (LAD) ligation. In comparison to the icariin groups, the MI group exhibited reduced EF and FS, along with elevated LVEDD and LVESD. Furthermore, the cardiac fibrosis levels in the MI group rats exhibited a considerable increase compared to those in the icariin group. Notably, the levels of Collagen I, Collagen III, MMP2, and MMP9 were significantly higher in the MI group than in the icariin group, with evident distinctions. Moreover, the expression levels of TGF-β, IL-13, p-Smad2, and p-Smad3 were notably upregulated in the MI group compared to the icariin group.Conclusion sIn an experimental rat model of MI, the administration of icariin resulted in the amelioration of both cardiac function and remodeling processes, operating through the intricate TGF-β1/Smad signaling pathway.
研究领域:
药理学
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心脏病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2018
·Vol. 10
·期 4
·239
·
IF 3.746
Qing Min,Jiaoyan Liu,Jing Li,Ying Wan,Jiliang Wu
Chitosan(CH)-polylactide(PLA) copolymers containing varied PLA percentages were synthesized using a group-protection method and one of them with solubility in water-based solvents was used to prepare CH-PLA/hyaluronic acid (HA) complex microspheres for the delivery of transforming growth factor-β1 (TGF-β1). An emulsification processing method was developed for producing TGF-β1-loaded CH-PLA/HA microspheres using sodium tripolyphosphate (TPP) as ionic crosslinker and the size of the microspheres was devised to the micron level in order to achieve high encapsulating efficiency. The encapsulating efficiency, swelling property and release administration of the microspheres could be synergistically regulated by PLA component, the applied TPP dose and the incorporated HA amount. In comparison to CH/HA microspheres, the CH-PLA/HA microspheres had greatly reduced TGF-β1 release rates and were able to administrate the TGF-β1 release at controlled rates over a significant longer period of time. The released TGF-β1 was detected to be bioactive when compared to the free TGF-β1. These results suggest that the presently developed CH-PLA/HA complex microspheres have promising potential in delivering TGF-β1 for cartilage repair applications where the applied TGF-β1 amount in the early stage needs to be low whilst the sustained TGF-β1 release at an appropriate dose in the later stage has to be maintainedKeywords:chitosan;polylactide;hyaluronic acid;microspheres;delivery of bioactive molecules;transforming growth factor-β1
研究领域:
生物材料
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药剂学
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组织工程
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DOI
PubMed
高影响因子
CHEMICAL & PHARMACEUTICAL BULLETIN
·
2024
·Vol. 72
·期 7
·669-675
·
IF 1.5
Xiongwei Deng,Qiang Li,Haitao Yuan,Hejun Hu,Shaoyong Fan
Tendon injury is a prevalent orthopedic disease that currently lacks effective treatment. Galangin (GLN) is a vital flavonoid found abundantly in galangal and is known for its natural activity. This study aimed to investigate the GLN-mediated molecular mechanism of tendon-derived stem cells (TDSCs) in tendon repair. The TDSCs were characterized using alkaline phosphatase staining, alizarin red S staining, oil red O staining, and flow cytometry. The effect of GLN treatment on collagen deposition was evaluated using Sirius red staining and quantitative (q)PCR, while a Western bot was used to assess protein levels and analyze pathways. Results showed that GLN treatment not only increased the collagen deposition but also elevated the mRNA expression and protein levels of multiple tendon markers like collagen type I alpha 1 (COL1A1), decorin (DCN) and tenomodulin (TNMD) in TDSCs. Moreover, GLN was also found to upregulate the protein levels of transforming growth factor β1 (TGF-β1) and p-Smad3 to activate the TGF-β1/Smad3 signaling pathway, while GLN mediated collagen deposition in TDSCs was reversed by LY3200882, a TGF-β receptor inhibitor. The study concluded that GLN-mediated TDSCs enhanced tendon repair by activating the TGF-β1/Smad3 signaling pathway, suggesting a novel therapeutic option in treating tendon repair.
研究领域:
骨科
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干细胞研究
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2022
·
IF 2.65
Fei Kong,Meng Zhao
Myocardial ischemia/reperfusion (MI/R) injury is a common clinical problem after myocardial infarction without effective therapy. Loureirin B (LrB) is a kind of flavonoid with anti-inflammatory and antifibrotic activities. However, the effect of LrB on MI/R and its underlying mechanism remains elusive. In the present study, a mouse model of MI/R was established by coronary artery occlusion. Administration of LrB (0.5 mg/kg or 1 mg/kg) for 4 weeks effectively improved left ventricular (LV) function and reduced myocardial infarction in MI/R mice. MI/R-induced expression of IL-6, TNF-α, and IL-1β in the hearts was reduced by LrB treatment. Histological analysis showed that LrB attenuated myocardial collagen deposition. LrB downregulated fibronectin, collagen I, collagen III, and α-SMA expression. Notably, LrB inhibited the expression of profibrotic plasminogen activator inhibitor-1 (PAI-1), transforming growth factor (TGF)-β1, TGF-β1R, and p-Smad2/3. Consistently, LrB inhibited the activation of TGF-β1/Smad signaling pathway and the expression of fibrosis-related proteins in angiotensin (Ang) II-treated cardiac fibroblasts (CFs). Overexpression of PAI-1 abolished the effects of LrB on Ang II-treated CFs, suggesting that LrB may function through regulating PAI-1. These results indicated that LrB may alleviate MI/R-induced myocardial fibrosis by inhibiting PAI-1/TGF-β1/Smad signaling pathway. Thus, LrB may be a potential drug in the treatment of MI/R injury.
研究领域:
心脏病学
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药理学
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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
CYTOTECHNOLOGY
·
2025
·Vol. 77
·期 2
·1-18
·
IF 1.7
Zhou Yi,Luan Fengwu,Feng Xiaonan,Yu Min,Li Lu,Guo Xiaoyan,Yin Xiaolong
Chronic kidney disease (CKD) often progresses to renal fibrosis, which is characterized by excessive extracellular matrix deposition and is also linked to ferroptosis. The present study investigated how TGF-β1 induces ferroptosis and thereby contributes to renal tubular epithelial cell fibrosis. Bioinformatics was employed to identify the differentially expressed genes relevant to renal fibrosis. An in vitro TGF-β1-induced fibrosis model of HK-2 cells was established, and the cell shape index was calculated. Fer-1, NAC, and PD98059 were utilized for targeted intervention, and their mechanisms were verified by transducing cells with WISP1-targeting shRNA lentivirus. Cell morphology was examined under a microscope, and cells were collected to determine the levels of ferroptosis-related factors (Fe 2+ , MDA, GSH, and LPO). Western blotting was performed to measure the levels of ERK1/2, WISP1, and ferroptosis indicators (GPX4 and hyperoxidized PRDX4). Flow cytometry was performed to determine the ROS levels and the rate of cell ferroptosis. TGF-β1 induced the transformation of HK-2 cells into fibroblast-like cells, leading to increased ROS levels, activation of the ERK1/2-WISP1 signaling pathway, and upregulation of ferroptosis and fibrosis-related factors. However, these effects could be effectively inhibited through pretreatment with Fer-1, NAC, and PD98059 individually, which further validated the involvement of the ERK1/2-WISP1 signaling pathway. In addition, WISP1 knockdown suppressed the cell transformation into fibroblast-like cells as well as the ferroptosis process, thereby reducing the expression levels of ferroptosis and fibrosis-related factors. The present study substantiated the process through which TGF-β1 elicits the production of ROS and triggers ferroptosis via the ERK1/2-WISP1 signaling pathway to facilitate the development of renal tubular epithelial cell fibrosis.
研究领域:
细胞生物学
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分子生物学
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医学
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产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2022
·Vol. 24
·期 1
·1-11
·
IF 2.751
Lianjie Xu,Yurong Zhang,Nengbo Ji,Yan Du,Tao Jia,Shanshan Wei,Wei Wang,Shan Zhang,Wenhui Chen
Tanshinone IIA (TIIA) is a major component extracted from the traditional herbal medicine Salvia miltiorrhiza and has been indicated to play a role in the treatment of organ fibrosis. However, the evidence supporting its antifibrotic effect is insufficient and the underlying mechanism is unclear. To investigate the therapeutic effect of TIIA on non‑alcoholic steatohepatitis‑related fibrosis (NASH‑F), the present study used a methionine choline deficiency diet to induce NASH‑F in rats, and explored the effect of TIIA on the transforming growth factor‑β1 (TGF‑β1)/Smad signaling pathway. Wistar rats were randomly divided into control, NASH‑F and TIIA groups. After 8 weeks of treatment, the levels of serum markers associated with liver function and fibrosis were measured, liver fat vacuoles and inflammation were assessed by haematoxylin and eosin staining, and liver fibrosis was assessed by Masson's trichrome staining. TGF‑β1, Smad2, Smad3, Smad7 and α‑smooth muscle actin (α‑SMA) mRNA expression, and TGF‑β1, Smad2/3, phosphorylated (p)‑Smad2/3, Smad7 and α‑SMA protein levels were determined. The results revealed that TIIA could remarkably ameliorate liver fat vacuoles and inflammation in NASH‑F rats, and could decrease the levels of serum aspartate aminotransferase, alanine aminotransferase, total bilirubin, total bile acid, hyaluronic acid, type Ⅳ collagen, laminin and type III collagen, while increasing the levels of total cholesterol and triglycerides; however, this was not statistically significance. TIIA markedly suppressed the increased TGF‑β1, Smad2, Smad3 and α‑SMA mRNA expression levels observed in the liver of NASH‑F rats, while it increased the mRNA expression level of Smad7. Similarly, TIIA suppressed the increased TGF‑β1, p‑Smad2/3 and α‑SMA protein levels observed in the liver of NASH‑F rats, while it increased the protein expression level of Smad7 in vitro and in vivo. TIIA had no significant cytotoxic effect at 10, 20, 40 and 80 µmol/l on human LX‑2 cell. In conclusion, the findings of the present study indicated that TIIA alleviated NASH‑F by regulating the TGF‑β1/Smad signaling pathway. TIIA may be a useful tool in the prevention and treatment of NASH‑F.
研究领域:
药理学
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肝病学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULES
·
2018
·Vol. 23
·期 1
·215
·
IF 3.098
Xinyan Peng,Chongshan Dai,Quanwen Liu,Junke Li,Jingru Qiu
This study aimed to investigate the protective effect of curcumin against carbon tetrachloride (CCl4)-induced acute liver injury in a mouse model, and to explain the underlying mechanism. Curcumin at doses of 50, 100 and 200 mg/kg/day were administered orally once daily for seven days prior to CCl4exposure. At 24 h, curcumin-attenuated CCl4induced elevated serum transaminase activities and histopathological damage in the mouse’s liver. Curcumin pre-treatment at 50, 100 and 200 mg/kg significantly ameliorated CCl4-induced oxidative stress, characterized by decreased malondialdehyde (MDA) formations, and increased superoxide dismutase (SOD), catalase (CAT) activities and glutathione (GSH) content, followed by a decrease in caspase-9 and -3 activities. Curcumin pre-treatment significantly decreased CCl4-induced inflammation. Furthermore, curcumin pre-treatment significantly down-regulated the expression of TGF-β1 and Smad3 mRNAs (bothp< 0.01), and up-regulated the expression of nuclear-factor erythroid 2-related factor 2 (Nrf2) and HO-1 mRNA (bothp< 0.01) in the liver. Inhibition of HO-1 attenuated the protective effect of curcumin on CCl4-induced acute liver injury. Given these outcomes, curcumin could protect against CCl4-induced acute liver injury by inhibiting oxidative stress and inflammation, which may partly involve the activation of Nrf2/HO-1 and inhibition of TGF-β1/Smad3 pathways.Keywords:curcumin;acute liver injury;Nrf2/HO-1 pathway;oxidative stress;TGF-β1/Smad3 pathway
研究领域:
药理学
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肝病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Materials Science
·
2024
·
IF 12.6
Ming Deng,Geliang Hu,Fan Liang,Qi Liao,Wanjun Ding,Bin He,Jianghua Ming,Hui Huang,Junqi Liu,Zhaohong Kong,Ping Xie
Objective To investigate the repair of spinal cord injury (SCI) in rats using 3D bioprinted decellularized extracellular matrix (dECM) hydrogel, neural stem cells (NSCs), and TGF-β1 monoclonal antibody. Methods The spinal cord-derived dECM hydrogel (SC-dECM-gel) was optimized for 3D printing. Rheological tests established a 3 % concentration as optimal. In vitro tests assessed the effects of TGF-β1 monoclonal antibody on NSC viability and differentiation. A rat SCI model was treated with the printed gel, and recovery was monitored using the Basso-Beattie-Bresnahan test and evoked potentials. Results The 3 % SC-dECM-gel showed superior rheological properties. TGF-β1 monoclonal antibody enhanced NSC survival and differentiation in vitro. In vivo, the 3D bioprinted gel significantly improved motor function and promoted neuronal regeneration. Conclusion 3D bioprinted SC-dECM-gel loaded with NSCs and TGF-β1 monoclonal antibody effectively restores motor function and promotes regeneration in SCI rats, offering a promising approach for SCI treatment.
研究领域:
再生医学
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神经科学
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生物材料学
✓ 已验证
DOI
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-19
·
IF 16.6
Da Xingwen,Li Ziyan,Huang Xiaofan,He Zuhan,Yu Yubing,Tian Tongtong,Xu Chengqi,Yao Yufeng,Wang Qing K.
Thoracic aortic aneurysm (TAA) is a localized or diffuse dilatation of the thoracic aortas, and causes many sudden deaths each year worldwide. However, there is no effective pharmacologic therapy. Here, we show that AGGF1 effectively blocks TAA-associated arterial inflammation and remodeling in three different mouse models (mice with transverse aortic constriction, Fbn1 C1041G/+ mice, and β-aminopropionitrile-treated mice). AGGF1 expression is reduced in the ascending aortas from the three models and human TAA patients. Aggf1 +/- mice and vascular smooth muscle cell (VSMC)-specific Aggf1 smcKO knockout mice show aggravated TAA phenotypes. Mechanistically, AGGF1 enhances the interaction between its receptor integrin α7 and latency-associated peptide (LAP)-TGF-β1, blocks the cleavage of LAP-TGF-β1 to form mature TGF-β1, and inhibits Smad2/3 and ERK1/2 phosphorylation in VSMCs. Pirfenidone, a treatment agent for idiopathic pulmonary fibrosis, inhibits TAA-associated vascular inflammation and remodeling in wild type mice, but not in Aggf1 +/- mice. In conclusion, we identify an innovative AGGF1 protein therapeutic strategy to block TAA-associated vascular inflammation and remodeling, and show that efficacy of TGF-β inhibition therapies require AGGF1.
研究领域:
心血管疾病
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Aging
·
2025
·
IF 19.4
Liu Liu,Wang Qianyue,Chen Meng,Zhou Haifeng,Li Xu,Yuan Ziqi,Hu Yong,Wang Chaoqun,Zhang Xiaohui,Hu Sheng,Wu Xiaoting,Li Meixin,Li Juanjuan,Chen Aijun,Yan Wei
Lung aging is a multifactorial series of molecular alterations that leads to gradual deterioration of lung function and increased vulnerability to cancer. Tumor communicates with host organs partially through extracellular vesicles; however, the mechanistic drivers and consequences of lung aging in the context of cancer remain unclear. Here we identify cancer cell-secreted dimethylarginine dimethylaminohydrolase-1 (DDAH1) protein induces citrulline accumulation and promotes lung fibrosis and aging. Mechanistically, our single-cell sequencing and genetic knockout mice evidence that citrulline availability elevation inhibits peptidyl arginine deiminase 4-mediated transforming growth factor-β1 (TGF-β1) citrullination, thereby inducing the TGF-β1/Smad3 signaling pathway in lung fibroblasts. Notably, vacuolar protein sorting assists the packaging of DDAH1 into the late endosomes. The administration of DDAH1 inhibitor reduces fibrosis and alleviates lung aging. Conclusively, our findings reveal tumor-derived DDAH1 protein contributes to citrulline accumulation to promote lung aging, shedding light on the treatment and diagnosis of tumors by inhibiting senescent lung fibroblasts.
研究领域:
肿瘤学
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呼吸系统生物学
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分子生物学
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细胞衰老
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信号转导
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转化医学
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肿瘤微环境
✓ 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）