CELLULAR SIGNALLING
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2025
·
IF 3.7
Biao-Hu Quan,Xin-Yue Liu,Zhou-Yan Li,Sheng-Zhong Han,Qi-Chao Cui,Shuang-Yan Chang,Si-Tong Lv,Xi-Jun Yin,Shuang Liang
Pulmonary fibrosis is a chronic interstitial lung disease characterized by irreversible, progressive lung scarring and eventual respiratory failure. Fibroblast activation plays a crucial role in the progression of pulmonary fibrosis. Transforming growth factor-β (TGF-β) signaling contributes to pulmonary fibrosis by regulating lung fibroblast activation. Currently, most studies focus on TGF-β1 regulatory effects on fibroblasts, with limited reports on myostatin (MSTN), another member of the same family. This study used MSTN gene knockout (MSTN −/− ) boars as animal models to explore MSTN regulatory effects on pulmonary fibrosis by modulating lung fibroblast activation. Studies have demonstrated that MSTN is significantly upregulated in the lungs during pulmonary fibrosis, promoting the activation of downstream Smad and AKT signaling pathways. MSTN −/− inhibits alveolar collapse and interstitial thickening in pulmonary fibrosis pigs and suppresses downstream Smad and AKT signaling. In vitro experiments showed that MSTN −/− inhibits lung fibroblast activation by blocking Smad/AKT signaling. These findings suggest that the MSTN/Smad/AKT signaling axis suppresses pulmonary fibrosis by inhibiting lung fibroblast activation, indicating that MSTN could be a potential therapeutic target for pulmonary fibrosis.
研究领域:
分子生物学
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医学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2018
·
IF 6.735
Min Hu,Fei Xiao,Qin-Fei Ke,Yang Li,Xiao-Dong Chen,Ya-Ping Guo
The development of nanoscience, nanohybrid technology and molecular biology provide an important strategy in the construction of novel bone scaffolds. Nanosized whitlockite (WH) and trace cerium (Ce) element exist widely in human bones; however their positive functions on bone cells/tissues still remain unknown. Inspired by the chemical components and nanostructures of bones, Ce-doped WH/chitosan (Ce-WH/CS) nanohybrid scaffolds were developed for new bone regeneration. The Ce-WH/CS scaffolds exhibited interconnected macropores with sizes of ∼300 μm, which facilitated cell adhesion and bone tissue in-growth. Ce-WH nanoparticles with sizes of 10–50 nm were dispersed on macroporous walls. The WH/CS scaffolds with or without doping Ce 3+ ions had non-toxicity to human adipose derived stromal cell (hADSCs). Interestingly, the Ce 3+ ions in the Ce-WH/CS scaffolds significantly improved osteogenic activity via activated SMAD signaling pathway, and up-regulated the expression of osteogenic-related genes including osteocalcin (OCN), osterix (OSX) and collagen 1A1 (COL1A1). Rat cranial defect models further demonstrated that Ce-WH/CS scaffolds remarkably accelerated material biodegradation and bone tissue growth compared to WH/CS scaffolds. The exciting finding revealed the positive functions of Ce-WH nanoparticles on bone tissues, and provided a promising platform for new bone regeneration.
研究领域:
纳米技术
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生物材料
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组织工程
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分子生物学
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DOI
高影响因子
Journal of Biomaterials and Tissue Engineering
·
2019
·Vol. 9
·期 6
·852-859
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IF 0.824
Wu Anqian,Li Xue,Yu Hongqiang,Xin Xirui,Ding Xinxin,Wang Yao,Zhou Yanmin
Titanium (Ti) and its alloys have been now widely used in the denture implantation. However, due to corrosion, the surface of the implants may release titanium (IV) (Ti(IV)) ions affecting the periimplant environment. Studies have found that Ti ions at high concentration may improve
the activity of osteoclasts and increase the inflammation, the mechanism of which is still unclear. Our study aimed to explore the effects of the Ti ions at low concentration (10 μmol/L) on the MC3T3-E1 cells which were of great osteogenic potential and whether the TGF-β/Smad
pathway played an important role during the process. We confirmed that 10 μmol/L Ti ions could improve the proliferation of MC3T3-E1 cells in a time-independent way. The expressions of Smad2/3, p-Smad2/3 and osteogenesis related genes were upregulated when the MC3T3-E1 cells cultured
in the medium with 10 mol/L Ti ions. In summary, low concentration of Ti ions (10 μmol/L) could promote the differentiation of MC3T3-E1 cells through the TGF-β/Smad pathway.
研究领域:
生物材料
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细胞生物学
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牙科种植学
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分子生物学
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DOI
高影响因子
CELLULAR AND MOLECULAR BIOLOGY
·
2024
·Vol. 70
·期 3
·95-101
·
IF 1.5
Shanfu Wang,Bing Xu,Heng Yin,Zhen Hua,Yang Shao,Jianwei Wang
Osteoporosis is a common chronic bone disorder in postmenopausal women. Ginsenosides are primary active components in ginseng and the effects of various ginsenoside variants in osteoporosis treatment have been widely revealed. We planned to explore the impact of ginsenoside Rc on bone resorption in an osteoporosis rat model. We used ovariectomized rats to assess the potential impact of ginsenoside Rc on osteoporosis. μ-CT was implemented for analyzing the microstructure of the distal left femur in rats. H&E staining together with Masson staining were applied for bone histomorphometry evaluation. ELISA kits were implemented to detect serum concentrations of TRACP-5b, OCN, CTX, as well as PINP. Ginsenoside Rc treatment lessened the serum levels of TRACP-5b as well as CTX, while increasing serum levels of OCN, and PINP of OVX rats. Moreover, we found that ginsenoside Rc contributed to the synthesis of type I collagen via increasing Col1a1 and Col1a2 levels in femur tissues of ovariectomized rats. Our findings also revealed that ginsenoside Rc activated the TGF-β/Smad pathway by increasing TGF-β as well as phosphorylated Smad2/3 protein levels. Ginsenoside Rc alleviates osteoporosis in rats through promoting the TGF-β/Smad pathway.
研究领域:
药理学
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骨科
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内分泌学
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分子生物学
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DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
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IF 5.7
Kuaitian Wang,Mengqi Jian,Yuhang Chen,Mengdi Du,Zhenhua Wang,Bo Xu,Ning Tang,Yongqiang Cheng,Jing Gan
The aim of this study was to determine the osteogenic activity and mechanism of soybean peptide VVELLKAFEEKF (SOP) and the potential relationship between SOP and transforming growth factor-β1 (TGF-β1). The results show that SOP promotes MC3T3-E1 cell proliferation by altering cell progression. SOP induced cell differentiation and mineralization in a dose-dependent manner at 0.7–7 μM. Moreover, SOP stimulates osteoblast differentiation, which may be achieved through the activation of p38-MAPK and Smad2/3 signaling pathways. Furthermore, treatment with a TβRI inhibitor (SB525334) inhibited the phosphorylation levels of p38 and Smad2/3, which indicates the involvement of TβRI in the process of osteoblast differentiation caused by SOP. Besides, in non-FBS-cultured MC3T3-E1 cells, SOP and TGF-β1 promoted the phosphorylation of Smad2/3 and alkaline phosphatase (ALP) activity, but the effect was lost when SOP was incubated separately, indicating that SOP stimulated osteoblast differentiation by promoting TGF-β1 activity. In vivo, SOP significantly restores bone mineral density loss and behavioral deficits in a model of glucocorticoid-induced osteoporosis (GIOP) in zebrafish. These results suggest that SOP may have the function of promoting bone remodeling and may be used as a potential active factor for functional food development to prevent osteoporosis.
研究领域:
生物学
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药理学
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医学研究
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产品关联
DOI
PubMed
高影响因子
GENE
·
2024
·
IF 2.6
Wen Zhong,Huanan Jia,Haiyan Zhu,Yuan Tian,Wei Huang,Qiyue Yang
Sarcopenia has become a prominent health problem among the elderly because of its adverse consequence, including physical disabilities and death. Fibro-adipogenic progenitors (FAPs) exhibit adipogenic and fibrogenic potencies and regulate skeletal muscle development, which plays important role in sarcopenia. Mairin, as an ingredient of Astragalus membranaceus, has the effect of anti-fibrosis. Therefore, we predicted that mairin targeted the fibrosis of FAPs and then affected sarcopenia. To verify our ideas, mairin (30 mg/kg/day or 60 mg/kg/day) was given to senescence accelerated mouse-prone 8 (SAMP8) mice by oral administration. Aging led to loss of weight, skeletal muscle mass, strength, and function, and an increase in muscle atrophy and fibrosis, while mairin administration inhibited physiological decline caused by aging. Similarly, mairin (20 μM or 40 μM) treatment enhanced FAP proliferation but blocked the differentiation into fibroblasts. Mechanically, mairin played an anti-fibrotic role via AMP-activated protein kinase-transforming growth factor beta-drosophila mothers against decapentaplegic protein (AMPK-TGF-β-SMAD) axis, as evidenced by increased phosphorylation of AMPKα and decreased TGF-β and phosphorylated-SMAD2/3. In addition, the potential target genes of mairin were explored by mRNA sequencing in our study. In conclusion, mairin may interfere with the AMPK/TGF-β/SMAD pathway to repress the fibrosis of FAPs and eventually ameliorate sarcopenia.
研究领域:
老年学
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药理学
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肌肉生物学
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DOI
PubMed
高影响因子
Human Cell
·
2023
·
IF 4.3
Hu Lianying,Cheng Zhen,Wu Lunan,Luo Liangliang,Pan Ping,Li Shujin,Jia Qiyu,Yang Ning,Xu Bin
Osteogenic differentiation plays important roles in the pathogenesis of osteoporosis. In this study, we explored the regulatory mechanism of histone methyltransferase SET domain bifurcated 1 (SETDB1) underlying the osteogenic differentiation in osteoporosis. The common osteoporosis-related genes were retrieved from the GeneCards, CTD, and Phenolyzer databases. The enrichment analysis was conducted on the candidate osteoporosis-related genes using the PANTHER software, and the binding site between transcription factors and target genes predicted by hTFtarget. The bioinformatics analyses suggested 6 osteoporosis-related chromatin/chromatin binding protein or regulatory proteins (HDAC4, SIRT1, SETDB1, MECP2, CHD7, and DKC1). Normal and osteoporosis tissues were collected from osteoporosis patients to examine the expression of SETDB1. It was found that SETDB1 was poorly expressed in osteoporotic femoral tissues, indicating that SETDB1 might be involved in the development of osteoporosis. We induced SETDB1 overexpression/knockdown, orthodenticle homeobox 2 (OTX2) overexpression, activation of Wnt/β-catenin or BMP-Smad pathways alone or in combination in osteoblasts or ovariectomized mice. The data indicated that SETDB1 methylation regulated H3K9me3 in the OTX2 promoter region and inhibited the expression of OTX2. Besides, the BMP-Smad and Wnt/β-catenin pathways were inhibited by OTX2, thereby resulting in inhibited osteogenic differentiation. Animal experiments showed that overexpressed SETDB1 could promote the increase of calcium level and differentiation of femoral tissues. In conclusion, upregulation of SETDB1 promotes osteogenic differentiation by inhibiting OTX2 and activating the BMP-Smad and Wnt/β-catenin pathways in osteoporosis.
研究领域:
分子生物学
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细胞生物学
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医学遗传学
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骨骼生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR CARCINOGENESIS
·
2025
·
IF 3.2
Fei Chen,Caitang Liu,Rongrong Jiang,Hao Wang
Colon cancer treatment remains a clinical challenge. Chaperonin containing TCP1 subunit 6 A (CCT6A) acts as an oncogene in multiple tumors. In this study, we investigated its roles in colon cancer cells. We analyzed CCT6A expression using single-cell datasets and the Gene Expression Profiling Interactive Analysis based on The Cancer Genome Atlas database. Immunohistochemistry, quantitative reverse transcription polymerase chain reaction, and western blot analysis were used to assess CCT6A expression levels in colon cancer tissues and cell lines. Additionally, specific roles of CCT6A in colon cancer was analyzed using cell counting kit-8, 5-ethynyl-2'-deoxyuridine staining, flow cytometry, wound healing, transwell, boron dipyrromethene staining, western blot analysis, and nude model mice. We found that CCT6A expression levels were significantly elevated in colon cancer tissues compared to those in normal tissues and predicted a worse prognosis. CCT6A induced proliferation, migration, invasion, epithelial-mesenchymal transition, and fatty acid synthesis and suppressed apoptosis in colon cancer cells. Mechanistically, CCT6A promoted colon cancer progression by increasing the cleavage of latency-associated peptide (LAP)-transforming growth factor-β1 (TGF-β1) to mature form of TGF-β and inducing Smad2/3 phosphorylation in colon cancer cells. Overall, CCT6A promoted colon cancer progression by modulating fatty acid metabolism and activating the TGF-β1/Smad signaling, serving as a potential therapeutic target for colon cancer.
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PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2022
·
IF 5.307
Tingting Ma,Huanli Cheng,Tongxi Li,Yifan Chen,Tianying Cai,Junjie Bai,Ziming Wu,Xianming Xia,Tiancheng Liang,Yichao Du,Wenguang Fu
Background Although liver fibrosis is a key pathologic process in many liver diseases, therapeutic approaches for inhibiting liver fibrosis are still very limited. N-Acetyl- l -tryptophan ( l -NAT) has a hepatoprotective effect via inhibiting the destruction of liver cells, enhancing cell viability and reducing the inflammation. However, the effect of l -NAT on liver fibrosis is not determined. Purpose The present study investigated the effect of l -NAT on liver fibrosis and explored it potential molecular mechanism. Methods To address this concern, this study was carried out via fibrotic mice model induced by CCl 4 and many approaches such as various histological staining methods, western blot assay, etc. Result l -NAT decreased the levels of alanine aminotransferase (ALT) and aspartate transaminase (AST) in fibrotic mice model induced by carbon tetrachloride (CCl 4 ). Histological staining showed that l -NAT ameliorated liver injury and fibrosis, and reduced the expression of α-smooth muscle actin (α-SMA) and Collagen I protein. l -NAT also attenuated apoptosis by down-regulating the level of pro-apoptotic protein Bax and up-regulating that of anti-apoptotic protein Bcl-2. Moreover, l -NAT inhibited the expressions of TGF-β1/SMAD and matrix metalloproteinase 9 (MMP9) proteins, and reversed the expression of YAP1 protein in CCl 4 -induced liver fibrosis. Conclusion These results clearly demonstrated that l -NAT attenuated CCl 4 -induced liver fibrosis in mice, and this protective mechanism might relate to TGF-β1/SMAD and Hippo/YAP1 signaling pathway. Thus, this study provided data basis for the prevention and treatment of liver fibrosis.
研究领域:
药理学
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肝病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
American Journal of Translational Research
·
2018
·
IF 3.061
Qian Tang,Minji Tong,Gang Zheng,Liyan Shen,Ping Shang,Haixiao Liu
The Masquelet’s induced membrane (IM) technique is widely used to treat large segmental bone defects due to its physical priority and biological function. However, the underlying molecular mechanism of the IM on bone formation remains unknown. In the present study, rat bone marrow-derived mesenchymal stem cells (BMSCs) were used as an in vitro model and bone morphogenetic protein 2 (BMP-2) was used as a positive control to evaluate the effects of the IM on the osteogenic differentiation of BMSCs. Although the IM group did not exhibit a significant increase in the expression of Runt-related transcription factor 2 (Runx2), Collagen I (Col I), osteocalcin (OCN) and alkaline phosphatase (ALP) relative to the BMP-2 administration, the IM was considerably effective compared with the untreated group. Mechanistically, we found that the IM activated the Smad and mitogen-activated protein kinase (MAPK) pathways, which was further confirmed by application of specific inhibitors of Smad1/5/8 (LDN-193189) and ERK1/2 (U0126). After the combined treatment of the IM and LDN-193189 as well as U0126, the IM-induced increase in Runx2, Col I, and OCN expression was significantly inhibited. These results suggest that IM promotes the osteogenic differentiation of rat BMSCs by activating the Smad1/5/8 and MAPK pathways.
研究领域:
骨科
·
干细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2019
·
IF 3.361
Chunyan Li,Xiao Sun,Ang Li,Min Mo,Zhongxi Zhao
Pulmonary fibrosis (PF) is a disease characterized by diffusing alveolar inflammation and alveolar structural disorders that ultimately lead to pulmonary interstitial fibrosis. S-allylmercaptocysteine (SAMC) as a water-soluble organosulfur garlic derivative exhibits efficient anti-inflammatory and anti-oxidative activities. In this study, we attempted to explore the function of SAMC in inhibiting bleomycin (BLM)-induced pulmonary fibrosis in mice. 0.035 U/g of BLM was intraperitoneally injected into mice twice per week for 4 weeks to induce fibrosis. SAMC (25 and 50 mg/kg) and N-acetylcysteine (NAC, 600 mg/kg) were given to mice for 28 days. The results indicate that SAMC could significantly ameliorate the pathological structure, and decrease inflammatory cell infiltration and pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) in BLM-induced pulmonary fibrosis mice. SAMC showed an anti-fibrosis effect by increasing anti-oxidants like HO-1, GSH and SOD as well as decreasing hydroxyproline (HYP) in BLM-induced mice. Mechanistic studies suggested that SAMC alleviated oxidative stress probably by impacting the Nox4/Nrf2 pathways, and played an anti-fibrosis role with decreasing the expression of α-SMA, collagen III, collagen I by suppressing the TGF-β1/Smad pathway. These findings indicate that SAMC may be partially responsible for the therapeutic effect on PF patients.
研究领域:
药理学
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肺科学
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免疫学
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病理学
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
·
2022
·Vol. 381
·期 3
·257-265
·
IF 4.402
Jian-Li Qiu,Guo-Feng Zhang,Yu-Na Chai,Xiao-Yan Han,Hai-Tao Zheng,Xiang-Feng Li,Fei Duan,Ling-Yan Chen
To investigate therapeutic target for ligustrazine during liver fibrosis in an ethanol-induced biliary atresia rat model and transforming growth factor-β (TGF-β) induced hepatic stellate cell activation cell model, and the underlying mechanism, a total of 30 rats were randomly assigned into five groups (n = 6 per group): control, sham, ethanol-induced biliary atresia model, model plus pirfenidone, and model plus ligustrazine groups. The liver changes were assessed using H&E and Masson staining and transmission electron microscopy. Expression of miR-145 and mRNA and protein levels of TGF-β/smads pathway-related proteins were detected. HSC-T6 cells were infected with LV-miR or rLV-miR-145 in the presence or absence of SMAD3 inhibitor SIS3 and treated with 2.5 ng/ml TGF-β1 and then with ligustrazine. Collected cells were subjected to detect the expression of miR-145 and mRNA and protein expression levels of TGF-β/smads pathway–related proteins. Ligustrazine rescued liver fibrogenesis and pathology for ethanol-caused bile duct injury, revealed by decreased α-smooth muscle actin and collagen I expression and liver tissue and cell morphology integrity. Further experiments showed that ligustrazine inhibited intrinsic and phosphorylated Smad2/3 protein expression and modification. Similar results were obtained in cells. In addition, ligustrazine altered miR-145 expression in both animal and cell models. Lentivirus mediated miR-145 overexpression and knockdown recombinant virus showed that miR-145 enhanced the TGF-β/Smad pathway, which led to hepatic stellate cell activation, and ligustrazine blocked this activation. This work validated that ligustrazine-regulated miR-145 mediated TGF-β/Smad signaling to inhibit the progression of liver fibrosis in a biliary atresia rat model and provided a new therapeutic strategy for liver fibrosis.
研究领域:
药理学
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肝病学
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分子生物学
·
细胞生物学
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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）