Molecular Medicine Reports
·
2016
·Vol. 13
·期 4
·3567-3573
·
IF 1.559
Ke Jiang,Guo Chun,Ziming Wang,Quanyin Du,Aimin Wang,Yan Xiong
Tendon adhesion is a common problem in the healing of injured tendons. The molecular mechanisms of the TGF-β/Smad signaling pathway have been determined, and the role of TGF-β has been well characterized in wound healing. However, the intracellular mechanism or downstream signals by which TGF-β3 modulates its effects on tendon healing have not been well elucidated. The aim of this study was to determine the effect of TGF‑β3 on the TGF-β/Smad signaling pathway in tenocytes. Quantitative polymerase chain reaction and western blot analysis were used to analyze the effect of TGF‑β3 on the regulation of the expression of Smad proteins in tenocytes. The results demonstrated that TGF‑β3 has no significant effect on the proliferation of tendon cells. The addition of TGF‑β3 to tenocytes can significantly downregulate the expression of Smad3 and upregulate the expression of Smad7 at the gene and protein levels. The results demonstrate that TGF‑β3 may regulate Smad3 and Smad7 proteins through the TGF-β/Smad signaling pathway to minimize extrinsic scarring. Thus, it may provide a novel approach to decrease tendon adhesion and promote tendon healing.
研究领域:
分子生物学
·
细胞生物学
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Huan Chen,Jin Liu,Jia Zhang,Yuqian Chen,Yan Wang,Yuanjie Qiu,Huizhong Hu,Limin Chai,Qianqian Zhang,Qingting Wang,Manxiang Li
Bromodomain-containing protein 4 (BRD4) is recognized as a member of the bromodomain and extraterminal (BET) family that is involved in the airway inflammation and airway remodeling of asthma. However, the underlying mechanisms of BRD4 in airway smooth muscle cells (ASMCs) proliferation and airway remodeling remain unclear. Primary cultured rat ASMCs and ovalbumin (OVA)-induced rat asthma models were applied to address these issues in the present study. We showed that transforming growth factor β1 (TGF-β1) increased the protein expression of ubiquitin specific peptidase 22 (USP22), which deubiquitinated BRD4 therefore increased its expression, and then resulted in the upregulation of glioma-associated oncogene homolog 1 (GLI1) and osteopontin (OPN) leading to ASMCs proliferation. We further confirmed that induction of TGF-β1 sequentially upregulated USP22, BRD4, GLI1 and OPN leading to airway remodeling in OVA-induced rat asthma models, targeting TGF-β1/USP22/BRD4/GLI1/OPN pathway axis effectively attenuated airway remodeling and asthma development. Our study provides novel sights to understand the role of TGF-β1/USP22/BRD4/GLI1/OPN axis in airway remodeling, and targeting this pathway might have potential value for the prevention and treatment of asthma.
研究领域:
医学
·
分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2026
·
IF 18.1
Li Chao,Chen Zehao,Li Wentao,Deng Ronghui,Huang Lingan,Song Yifan,Wang Yiqun,Cui Guoqing,Liu Huawei,Yu Jiakuo
Excessive transforming growth factor-β1 (TGF-β1) signaling is a key driver of the pathological processes of fibrosis and matrix disorganization in tendinopathy, yet current treatments do not directly target this fibrotic microenvironment. Here we show that a self-assembling peptide composed entirely of natural amino acids, AsPep-FTSQ, can locally capture TGF-β1 and remodel the pathological tendon niche. Injecting AsPep-FTSQ into rat and beagle models of tendinopathy resulted in the formation of an interconnected nanofibrous network in situ that selectively sequesters excess TGF-β1. This network suppresses pro-fibrotic signaling, limits pathological tendon cell (TC) state transitions, and promotes collagen realignment. These effects improve tendon structure and functional repair across species. This fully natural, self-assembling peptide composed of amino acids provides a modular strategy for local cytokine sequestration and suggests a therapeutic approach for tendinopathy and potentially other fibrotic soft-tissue disorders.
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Hui-Wen Yang,Yan Lan,An Li,Han Wu,Zi-Wei Song,Ai-Ling Wan,Yue Wang,Shi-Bao Li,Shuai Ji,Zhong-Cheng Wang,Xin-Yu Wu,Ting Lan
Background: Ovarian cancer (OC) is the second most common gynecological malignancy and has a high mortality rate. The current chemotherapeutic drugs have the disadvantages of drug resistance and side effects. Myricetin, a kind of natural compound, has the advantages of easy extraction, low price, and fewer side effects. Multiple studies have demonstrated the anti-cancer properties of myricetin. However, its impact on OC is still unknown and needs further investigation. Therefore, this study aimed to elucidate the mechanism by which myricetin suppresses transforming growth factor-β (TGF-β) -induced epithelial-to-mesenchymal transition (EMT) in OC through in vivo and in vitro experiments. Methods: In vitro experiments were conducted to evaluate the effects of myricetin on cell proliferation and apoptosis using CCK8 assay, plate clonal formation assay, and flow cytometry. Western blot was employed to evaluate the expression levels of caspase-3, PARP, and the MAPK/ERK and PI3K/AKT signaling pathways. Wound healing, transwell, western blot and immunofluorescence assay were used to detect TGF-β-induced cell migration, invasion, EMT and the levels of Smad3, MAPK/ERK, PI3K/AKT signaling pathways. Additionally, a mouse xenograft model was established to verify the effects of myricetin on OC in vivo . Results: Myricetin inhibited OC proliferation through MAPK/ERK and PI3K/AKT signaling pathways. Flow cytometry and western blot analyses demonstrated that myricetin promoted apoptosis by increasing the expression of cleaved-PARP and cleaved-caspase-3 and the ratio of Bax/Bcl-2 in OC. Furthermore, myricetin suppressed the TGF-β-induced migration and invasion by transwell and wound healing assays. Mechanistically, western blot indicated that myricetin reversed TGF-β-induced metastasis through Smad3, MAPK/ERK and PI3K/AKT signaling pathway. In vivo , myricetin significantly repressed OC progression and liver and lung metastasis. Conclusion: Myricetin exhibited inhibitory effects on OC progression and metastasis both in vivo and in vitro . And it also reversed TGF-β-induced EMT through the classical and non-classical Smad signaling pathways.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
HUMAN & EXPERIMENTAL TOXICOLOGY
·
2020
·Vol. 39
·期 5
·683-695
·
IF 2.067
Y Chen,Q Zhang,Y Zhou,Z Yang,M Tan
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with high morbidity and mortality. miR-182-5p is overexpressed in several fibrosis-related diseases but its effect in pulmonary fibrosis has not been reported yet. To investigate the function of miR-182-5p in pulmonary fibrosis, we established bleomycin (BLM)-induced fibrotic mice model and transforming growth factor-β1 (TGF-β1)-treated human embryonic lung fibroblasts model. In this study, miR-182-5p was highly expressed in pulmonary tissues of BLM-induced fibrotic mice. The content of hydroxyproline and TGF-β1 was decreased by downregulating the expression of miR-182-5p, indicating that fibrosis was alleviated in mice treated with Lentivirus-anti-miR-182-5p.Quantification of fibrosis-related proteins demonstrated that downregulation of miR-182-5p inhibited the expression of profibrotic proteins (fibronectin, α-smooth muscle actin, p-Smad2/p-Smad3) as well as enhanced the level of Smad7. In vitro assays validated that miR-182-5p was induced by TGF-β1 with the function of promoting fibrosis. In dual-luciferase reporter assay, Smad7 was demonstrated to be negatively regulated by miR-182-5p. Moreover, the effect of knocking down miR-182-5p on inhibiting fibrosis was achieved by upregulating the expression of Smad7. Therefore, miR-182-5p can be regarded as a biomarker of IPF and its inhibition may be a promising therapeutic approach in treating IPF.
研究领域:
肺病学
·
分子生物学
·
病理学
✓ 已验证
DOI
PubMed
高影响因子
CELL DEATH AND DIFFERENTIATION
·
2023
·
IF 12.4
Xu Ya-Jie,Dai Shang-Kun,Duan Chun-Hui,Zhang Zi-Han,Liu Pei-Pei,Liu Cong,Du Hong-Zhen,Lu Xu-Kun,Hu Shijun,Li Lei,Teng Zhao-Qian,Liu Chang-Mei
The ability of neural stem/progenitor cells (NSPCs) to proliferate and differentiate is required through different stages of neurogenesis. Disturbance in the regulation of neurogenesis causes many neurological diseases, such as intellectual disability, autism, and schizophrenia. However, the intrinsic mechanisms of this regulation in neurogenesis remain poorly understood. Here, we report that Ash2l (Absent, small or homeotic discs-like 2), one core component of a multimeric histone methyltransferase complex, is essential for NSPC fate determination during postnatal neurogenesis. Deletion of Ash2l in NSPCs impairs their capacity for proliferation and differentiation, leading to simplified dendritic arbors in adult-born hippocampal neurons and deficits in cognitive abilities. RNA sequencing data reveal that Ash2l primarily regulates cell fate specification and neuron commitment. Furthermore, we identified Onecut2 , a major downstream target of ASH2L characterized by bivalent histone modifications, and demonstrated that constitutive expression of Onecut2 restores defective proliferation and differentiation of NSPCs in adult Ash2l -deficient mice. Importantly, we identified that Onecut2 modulates TGF-β signaling in NSPCs and that treatment with a TGF-β inhibitor rectifies the phenotype of Ash2l -deficient NSPCs. Collectively, our findings reveal the ASH2L-Onecut2-TGF-β signaling axis that mediates postnatal neurogenesis to maintain proper forebrain function.
研究领域:
神经科学
·
分子生物学
·
发育生物学
✓ 已验证
DOI
PubMed
高影响因子
Acta Cirurgica Brasileira
·
2018
·Vol. 33
·期 3
·207-215
·
IF 0.933
Wu Jing,Pan Lin,Jin Xueqin,Li Weihua,Li Hongbing,Chen Jianmao,Yang Wen
Purpose: To investigate whether oxymatrine (OMT) prevents hepatic fibrosis in rats by regulating liver transforming growth factor β1 (TGF-β1) level. Methods: Hepatic fibrosis was induced in rats by thioacetamide (TAA). Blood was collected at the end of week 12 to determine the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and glutathione (GSH). Changes in liver tissue were observed after hematoxylin-eosin (HE) staining. Results: Fibrosis was confirmed by Masson’s collagen staining. Liver TGF-β1 level was determined by ELISA. OMT significantly reduced serum ALT and AST but increased GSH levels in rats with hepatic fibrosis. Moreover, it significantly improved liver histology in rats with TAA-induced hepatic fibrosis. It significantly decreased liver TGF-β1 level compared to that in the untreated group. It also significantly reduced collagen deposition in rats. Conclusion: Oxymatrine is effective in protecting rats from thioacetamide-induced hepatic fibrosis by regulating TGF-β1 expression.
研究领域:
药理学
·
肝脏病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOLOGY OF REPRODUCTION
·
2025
·Vol. 114
·期 3
·871-882
·
IF 3
Yang Jinjin,Ren Li,Gu Xiaoli,Wang Lu,Cui Jinquan
Intrauterine adhesion (IUA) is an adhesion of the uterine cavity or cervical canal resulting from damage to the basal layer of the endometrium， usually accompanied by fibrosis of the endometrium. This study analyzed endometrial samples from three IUA patients and three healthy control participants and screened for differentially expressed genes (DEGs) using RNA-seq and bioinformatics techniques. A total of 2402 DEGs were identified in endometrial tissues compared to normal endometrial tissues, among which microfibrillar-associated protein 5 (MFAP5) was upregulated in IUA tissues (log2FoldChange = 3.81, P = 1.98E-08). Meanwhile, clinical tissue specimens revealed remarkably up-regulated MFAP5 expression in endometrial tissues of IUA patients, accompanied by increases in the fibrosis markers collagen type I A 1 and α-smooth muscle actin. A mouse model of IUA was constructed by mechanical curettage. Histopathology revealed that MFAP5 downregulation attenuated IUA model-induced reduction in endometrial gland number and collagen deposition. Furthermore, MFAP5 knockdown alleviated the increase in embryo uptake ratio and the decrease in embryo and placental weight in IUA model. In vitro, the expression of fibrosis indicators was upregulated in Ishikawa cells treated with 5 ng/mL transforming growth factor-β1 (TGF-β1), while MFAP5 siRNA reduced levels of the endometrial fibrosis markers. RNA-seq analysis was performed on normal-treated and MFAP5 knockdown-treated TGF-β1-induced cell lines. Enrichment analysis revealed that the MFAP5 siRNA may be involved in microfibril formation, collagen deposition, and the TGF-β pathway. These results further confirm the potential role of MFAP5 in promoting endometrial fibrosis, which provides new insight for the clinical treatment of IUA.
✓ 已验证
DOI
高影响因子
ONCOGENE
·
2026
·
IF 9.1
Tian Shuai,Gu Shuchen,Sun Shuangwu,Wang Zhaoyang,Zhao Yingming,Yuan Bo,Liu Xia,Zhao Bin,Xu Pinglong,Cao Jin,Xiao Mu,Yu Yi,Feng Xin-Hua
Transforming growth factor-β (TGF-β) is a multifunctional cytokine that regulates cell proliferation, differentiation, migration, and apoptosis. It is generally accepted that TGF-β induces cellular responses through Smad-dependent gene transcription. However, the underlying mechanisms that modulate the transcriptional activities of Smads are not yet fully understood. Here, we identify BRD2, a member of the bromodomain and extraterminal (BET) family, as a key transcriptional coactivator for Smad3. BRD2 physically interacts with Smad3 through a newly identified Smad3-binding region (SBR). This BRD2-Smad interaction enhances Smad’s association with chromatin and amplifies its transcriptional activity, playing a vital role in TGF-β transcriptional and tumor-suppressive responses. Our findings establish BRD2 as an important modulator of TGF-β signaling and suggest that it may serve as a potential target for TGF-β-related diseases.
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2026
·
IF 5.9
Xifan Zheng,Bo Yu,Yuansong Song,Yeping Chen,Zeming Li,Jun Yao
Objective Osteoarthritis (OA) involves an inflammatory imbalance, yet key mediators and their interplay with potential therapeutics like artemisinin (ART) remain poorly understood. This study aimed to systematically investigate these relationships using Mendelian randomization and to decipher their functional interactions through cellular and molecular experiments, complemented by network pharmacology and molecular docking analyses. Methods Using the Mendelian randomization (MR) method, we integrated independent exposure–outcome genome-wide association study data to evaluate the causal association between inflammatory cytokines and OA. Chondrocytes were treated with IL-1β, TGF-β1 (5 μg/mL), and ART (4 μg/mL) for 24 hours. Cell proliferation was assessed using CCK-8 and EdU assays, and gene/protein expression was analyzed via RT-qPCR, Western blotting, and immunofluorescence staining. In parallel, network pharmacology was performed to identify putative ART targets related to OA and to characterize enriched pathways and hub genes through GO/KEGG enrichment and protein–protein interaction (PPI) analyses. Molecular docking was further conducted to evaluate the binding feasibility between ART and the catabolic mediator MMP-13. Results MR revealed a positive association between TGF-β1 and OA risk (OR = 1.0526, P = 0.0182). Functionally, ART significantly enhanced chondrocyte proliferation, whereas TGF-β1 inhibited it. ART downregulated IL-1β and MMP13 expression, while TGF-β1 upregulated them, indicating opposing effects in OA chondrocytes. Network pharmacology suggested that ART-related OA targets were enriched in inflammation-associated processes and signaling pathways (e.g., MAPK signaling), with PPI analysis highlighting inflammatory signaling hubs (e.g., JAK/STAT-related nodes). Consistently, molecular docking demonstrated favorable binding of ART within the MMP-13 active pocket, supporting the structural feasibility of an ART–MMP-13 interaction. Conclusion This study demonstrates that TGF-β1 plays an important pathogenic role in OA, as supported by MR and in vitro evidence, while ART exhibits anti-inflammatory and anti-catabolic effects by counteracting TGF-β1–driven inflammatory responses. Network pharmacology and docking analyses further suggest multi-target pathway regulation and a potential interaction with MMP-13. ART may represent a viable therapeutic candidate for OA; however, further studies are required to validate direct targets and elucidate tissue-specific mechanisms.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2018
·Vol. 6
·期 9
·2472-2486
·
IF 5.831
Qiyu Zhu,Ming Jiang,Qiang Liu,Shina Yan,Longbao Feng,Yong Lan,Guiqiu Shan,Wei Xue,Rui Guo
Burn wounds are associated with a series of risks, such as infection and pathologic scar tissue formation, which significantly delay wound healing and lead to complications. In this study, we successfully fabricated a dextran-hyaluronic acid (Dex-HA) hydrogel enriched with sanguinarine (SA) incorporated into gelatin microspheres (GMs), which had high porosity, good swelling ratio, enhanced NIH-3T3 fibroblast cell proliferation, and sustained SA release profile. The in vitro degradation results indicate that the SA/GMs/Dex-HA hydrogel can be degraded. The in vitro antibacterial tests showed that the SA/GMs/Dex-HA hydrogel can inhibit methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli). We evaluated the wound-healing effects and antibacterial properties of SA/GMs/Dex-HA hydrogels in a rat full-thickness burn infection model. The hematoxylin–eosin (H&E) and Masson's trichrome staining results of the SA/GMs/Dex-HA hydrogel showed that it improved re-epithelialization and enhanced extracellular matrix remodeling, and immunohistochemistry results showed that the expression of TGF-β1 and TNF-α was decreased, while the TGF-β3 expression was increased. Our findings suggest that the SA/GMs/Dex-HA hydrogel provides a potential way for infected burn treatment with high-quality and efficient scar inhibition.
研究领域:
生物医学工程
·
药剂学
·
伤口愈合
·
材料科学
·
传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
IBRO Neuroscience Reports
·
2025
·
IF 2.9
Penghui Cao,Shichuan Shen,Ziyan Fang,Junjie Tan,Jinwei Wang,Nannan Pan
Objective This study aims to investigate the role of the TGF-β/Smad Signaling in depression comorbidity in epileptic individuals and to evaluate the effect of losartan on depressive symptoms. Methods Li-Popilocarpine was used to induce status epilepticus (SE) in rats. The rats in which SE was successfully induced were randomly divided into the SE saline group and the SE losartan group. Then, the rats in the different groups were given the corresponding interventions for 20 days. After the intervention, the depression levels of the rats in each group were evaluated. Upon completion of the intervention, brain tissue was collected for comprehensive assessment of TGF-β mRNA levels, TGF-β/Smad Signaling-related protein expression, and GFAP⁺ astrocyte density in the rat hippocampus. Results The depression-like behavior of SE rats was more obvious than that of control rats. TGF-β mRNA, p-Smad2, p-Smad3 and GFAP⁺ astrocyte expression levels were significantly greater in SE rats than in control rats. Compared with the SE-saline group, the depression-like behavior of the SE-losartan group improved. The expression levels of TGF-β mRNA p-Smad2, p-Smad3 and GFAP⁺ astrocyte expression in the SE-losartan group rats were lower than those in the SE-saline group. Conclusion The TGF-β/Smad Signaling is an important Signaling leading to depression-like behavior in epileptic rats. Losartan is a drug that can significantly improve the depression-like behavior of epileptic rats by regulating the TGF-β/Smad Signaling. Findings in this study support losartan as a repurposable central nervous system drug for comorbid depression in epilepsy, warranting further clinical investigation.
研究领域:
神经病学
·
精神病学
·
分子神经生物学
·
信号转导
·
转化医学
·
药物重定位
✓ 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）