NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
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2024
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IF 3.1
Sun Hui,Wang ZiTong,Tu BingHua,Shao ZiChen,Li YiDan,Han Di,Jiang YinJie,Zhang Peng,Zhang WeiChang,Wu YunYan,Wu XiaoMing,Liu Chi-Ming
Type 2 diabetes mellitus (T2DM) is a metabolic disease. Diabetes increases the risk of benign prostatic hyperplasia (BPH). Capsaicin is extracted from chili peppers and possesses many pharmacological properties, including anti-diabetic, pain-relieving, and anti-cancer properties. This study aimed to investigate the effects of capsaicin on glucose metabolism and prostate growth in T2DM mice and uncover the related mechanisms. Mice model of diabetes was established by administering a high-fat diet and streptozotocin. Oral administration of capsaicin for 2 weeks inhibited prostate growth in testosterone propionate (TP)-treated mice. Furthermore, oral administration of capsaicin (5 mg/kg) for 2 weeks decreased fasting blood glucose, prostate weight, and prostate index in diabetic and TP-DM mice. Histopathological alterations were measured using hematoxylin & eosin (H&E) staining. The protein expression of 5α-reductase type II, androgen receptor (AR), and prostate-specific antigen (PSA) were upregulated in diabetic and TP-DM mice, but capsaicin reversed these effects. Capsaicin decreased the protein expression of p-AKT, insulin-like growth factor-1 (IGF-1), IGF-1R, and the receptor for advanced glycation end products (RAGE) in diabetic and TP-DM mice. Capsaicin also regulated epithelial-mesenchymal transition (EMT) and modulated the expression of fibrosis-related proteins, including E-cadherin, N-cadherin, vimentin, fibronectin, α-SMA, TGFBR2, TGF-β1, and p-Smad in TP-DM mice. In this study, capsaicin alleviated diabetic prostate growth by attenuating EMT. Mechanistically, capsaicin affected EMT by regulating RAGE/IGF-1/AKT, AR, and TGF-β/Smad signalling pathways. These results provide with new therapeutic approach for treating T2DM or T2DM-induced prostate growth.
研究领域:
药理学
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内分泌学
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糖尿病
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前列腺健康
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信号转导
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DOI
PubMed
高影响因子
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY
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2023
·
IF 1.9
Wenchao Pan,Yadong Wang,Caiyan Zhao
Objective To explore the protective effect and related mechanism of miR-140-5p on liver fibrosis by interfering with TGF-β/Smad signaling pathway.Methods Liver fibrosis mice models were established by intraperitoneal injection of CCL4. Hematoxylin and eosin (HE) staining was used to detect the structural and morphological changes of the liver. Masson staining was used to detect collagen deposition. Human hepatic stellate cells (HSCs, LX-2) were transfected with miR-140-5p mimic or inhibitor then treated with TGF-β1. The qRT-PCR and Western blotting was used to detect the expression of related molecules. The luciferase reporter assay was used to identify the target of miR-140-5p.Results Our results indicated that miR-140-5p expression was downregulated in fibrotic liver tissues of model mice and LX-2 cells treated with TGF-β1. The overexpression of miR-140-5p decreased the expression of collagen1(COL1) and α-smooth muscle actin(α-SMA), inhibited the phosphorylation of Smad-2/3 (pSmad-2/3) in LX-2 cells. Conversely, the knockdown of miR-140-5p upregulated COL1 and α-SMA expression, increased Smad-2/3 phosphorylation. A dual-luciferase reporter assay showed that TGFβR1 was a target gene of miR-140-5p. The overexpression of miR-140-5p suppressed TGFβR1 expression in LX-2 cells. Additionally, knockdown of TGFβR1 decreased the expression of COL1 and α-SMA. Conversely, the overexpression of TGFβR1 reversed the inhibitory effect of miR-140-5p upregulation on expression of COL1 and α-SMA.Conclusion miR-140-5p bound to TGFβR1 mRNA 3′-untranslated region(3′UTR) and inhibited the expression of TGFβR1, pSmad-2/3, COL1 and α-SMA, thereby exerting a potential therapeutic effect on hepatic fibrosis.
研究领域:
分子生物学
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肝病学
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药理学
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DOI
PubMed
高影响因子
HUMAN & EXPERIMENTAL TOXICOLOGY
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2020
·Vol. 39
·期 5
·683-695
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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
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分子生物学
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病理学
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DOI
PubMed
高影响因子
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
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2026
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IF 4.5
Zhanpeng Tang,Jian Li,Rongyang Li,Luyuan Ma,Renchang Zhao,Zhenguo Sun,Hui Tian
Esophageal squamous cell carcinoma (ESCC) represents a common malignancy of the digestive system. Circular RNAs (circRNAs) are a distinct class of single-stranded non-coding RNAs that are essential in the progression of various tumors given that they can act as microRNA (miRNA) sponges in a manner similar to that of mRNAs. In this study, circ_0006156 is screened to be highly expressed in ESCC tissues through high-throughput sequencing and quantitative real-time polymerase chain reaction. Subsequent in vitro and in vivo experiments are conducted to validate its biological functions. Furthermore, the regulatory relationships among circ_0006156, miR-202-5p, and TGFBR1 are investigated using RNA antisense purification, miRNA sequencing, RNA immunoprecipitation, fluorescence in situ hybridization, dual-luciferase reporter assay, and bioinformatics analyses. The results show significant overexpression of circ_0006156 in ESCC tissues, with relatively shorter overall survival observed in patients with high circ_0006156 expression. circ_0006156 is further identified to directly bind to miR-202-5p. miR-202-5p inhibits the proliferation, migration, and invasion of ESCC cells in vitro and partially rescues the effects induced by circ_0006156. Consistent results are reported by subcutaneous xenograft tumor experiments in nude mice. In addition, circ_0006156 is confirmed to act as an endogenous sponge for miR-202-5p, which results in a relieved suppression of its target gene TGFβR1 . In summary, circ_0006156 can regulate TGFβR1 expression by sponging miR-202-5p, which may further activate the TGFβ/Smad pathway and promote ESCC progression. Collectively, circ_0006156 functions as a novel oncogenic RNA in ESCC and may serve as a potential tumor marker.
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DOI
PubMed
高影响因子
Molecular Medicine Reports
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2016
·Vol. 13
·期 4
·3567-3573
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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
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细胞生物学
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骨科
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产品关联
DOI
PubMed
高影响因子
IBRO Neuroscience Reports
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2025
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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
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精神病学
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分子神经生物学
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信号转导
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转化医学
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药物重定位
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产品关联
DOI
PubMed
高影响因子
Frontiers in Medicine
·
2026
·
IF 3.6
Wenbing Lai,Lurun Wang,Wei Tang,Yuze Liu
Background Skin photoaging, primarily caused by chronic ultraviolet B (UVB) exposure, is characterized by cellular senescence and extracellular matrix (ECM) degradation. Suppression of transforming growth factor-β (TGF-β)/Smad signaling plays a critical role in UVB-induced collagen loss and impaired skin repair. Azelaic acid (AzA), a clinically established dermatological agent with antioxidant and anti-inflammatory properties, has been reported to maintain skin homeostasis; however, its mechanistic role in protecting against UVB-induced photoaging remains unclear. Objective This study aimed to investigate whether AzA alleviates UVB-induced photoaging in keratinocytes and to determine whether its protective effects are mediated through the restoration of Smad-dependent TGF-β signaling. Methods An in vitro UVB-induced photoaging model was established using HaCaT keratinocytes. Following UVB irradiation, cells were treated with AzA. Cell viability and cytotoxicity were evaluated using CCK-8 and LDH assays, respectively. Cellular senescence was assessed by senescence-associated β-galactosidase staining. ECM-related markers were measured by ELISA. TGF-β/Smad signaling activity was analyzed by Western blotting, quantitative real-time PCR, and immunofluorescence. The selective TGF-β/Smad inhibitor SB431542 was used to verify pathway dependence. A keratinocyte–fibroblast conditioned medium model was also employed to assess the paracrine regulation of fibroblast ECM metabolism. Results AzA significantly attenuated UVB-induced cellular senescence and partially restored cell viability in HaCaT cells. It significantly increased pro-collagen I levels and reduced MMP-1 levels, indicating the restoration of ECM-related protein balance. Mechanistically, AzA reversed UVB-induced suppression of TGF-β/Smad signaling by enhancing Smad2/3 phosphorylation, decreasing Smad7 expression, promoting the nuclear translocation of phosphorylated Smad2/3, and restoring Smad-dependent transcription. Pharmacological inhibition of TGF-β/Smad signaling largely abrogated these protective effects. Conditioned medium from AzA-treated keratinocytes also improved ECM-related responses in fibroblasts in a Smad-dependent manner. Conclusion AzA alleviates UVB-induced photoaging by restoring Smad-dependent TGF-β signaling, preserving ECM homeostasis, and modulating epidermal–dermal crosstalk in vitro. These findings provide mechanistic support for the potential application of AzA in anti-photoaging strategies.
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DOI
PubMed
高影响因子
Chemical Biology & Drug Design
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2025
·Vol. 106
·期 6
·e70226
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IF 3.3
Yaqiong Wang,Li Ma
Pachymic acid exerts antitumor effects against renal cell carcinoma and breast, lung, and pancreatic cancers; however, its specific inhibitory effect on endometrial cancer progression remains unclear. Therefore, in this study, we investigated the antitumor effects of pachymic acid against endometrial cancer using cell counting kit 8, flow cytometry, wound healing, transwell, cycloheximide chase, and western blot assays. Notably, pachymic acid significantly suppressed the viability, proliferation, and migration of endometrial cancer cells. Nuclear receptor subfamily 3 group C member 1 (NR3C1) was identified as its potential target against endometrial cancer. Pachymic acid promoted NR3C1 degradation. However, NR3C1 overexpression reversed the inhibitory effects of pachymic acid on the proliferation and migration of endometrial cancer cells. Furthermore, an association was observed between NR3C1 expression and the transforming growth factor beta (TGF-β) pathway. NR3C1 knockdown and pachymic acid treatment reduced protein levels of TGF-β1 and p-Smad2/3. TGF-β pathway inhibitor galunisertib reversed the NR3C1 overexpression-induced increase in endometrial cancer cell migration. Collectively, our findings suggest that pachymic acid suppresses endometrial cancer cell migration by inhibiting the NR3C1/TGF-β/Smad signaling pathway, highlighting its potential as a therapeutic agent for endometrial cancer.
研究领域:
肿瘤学
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分子生物学
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药理学
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细胞生物学
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天然产物研究
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PubMed
高影响因子
TOXICOLOGY
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2022
·
IF 4.571
Peng Lin,Xu Tong,Fan Xue,Chi Qianru,Tang Xinyu,Li Zhe,Bai Zhikun,Li Shu
Polystyrene nanoplastics (PS NPs) contamination is a serious problem for human and animal health. Excessive exposure to PS NPs can affect the structure and function of the heart. And lipopolysaccharide (LPS) induces myocardial damage , leading to myocardial fibrosis (MF). To investigate whether PS NPs exacerbate LPS-induced myocardial autophagy and fibrosis , we established in vivo and in vitro models of PS NPs/LPS exposure alone and in combination. We found that PS NPs/LPS exposure disrupts myocardial structure, significantly increases reactive oxygen species (ROS), triggers oxidative stress , promotes TGF-β1/Smad pathway activation, and leads to elevated levels of fibrotic proteins and collagen. Meanwhile, activation of AMPK/mTOR/ULK1 signaling pathway induced autophagy onset, and combined exposure of PS NPs/LPS exacerbated MF and autophagy. H9C2 cells were used for in vitro experiments, and the experimental results showed that the addition of TGF-β receptor inhibitor LY2109761 to the exposed group not only inhibited the upregulation of fibrotic genes but also effectively reduced the expression of autophagic signals, indicating that combined exposure of PS NPs and LPS mediates and regulates cardiac autophagy through TGF-β1. The above results suggest that PS NPs exacerbate LPS-induced MF and autophagy in mice via ROS/TGF-β1/Smad. Our study provides some new evidence to clarify the potential mechanisms of PS NPs-induced cardiotoxicity.
研究领域:
毒理学
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心脏病学
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纳米技术
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细胞生物学
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DOI
PubMed
高影响因子
Oncotarget
·
2017
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IF 5.168
Ling Zhou,Xiaoying Dong,Linlin Wang,Lanlan Shan,Ting Li,Wanfu Xu,Yan Ding,Mingqiang Lai,Xiaojun Lin,Meng Dai,Xiaochun Bai,Chunhong Jia,Hang Zheng
Although many advances have been made in understanding the pathogenesis of liver fibrosis, few options are available for treatment. Casticin, one of the major flavonoids in Fructus Viticis extracts, has shown hepatoprotective potential, but its effects on liver fibrosis are not clear. In this study, we investigated the antifibrotic activity of casticin and its underlying mechanism in vivo and in vitro . Male mice were injected intraperitoneally with carbon tetrachloride (CCl 4 ) or underwent bile duct ligation (BDL) to induce liver fibrosis, followed by treatment with casticin or vehicle. In addition, transforming growth factor-β1(TGF-β1)-activated LX-2 cells were used. In vivo experiments showed that treatment with casticin alone had no toxic effect while significantly attenuating CCl 4 -or BDL-induced liver fibrosis, as indicated by reductions in the density of fibrosis, hydroxyproline content, expression of α-SMA and collagen α1(I) mRNA. Moreover, casticin inhibited LX2 proliferation, induced apoptosis in a time- and dose-dependent manner in vitro . The underlying molecular mechanisms for the effect of casticin involved inhibition of hepatic stellate cell (HSC) activation and reduced the expression of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 resulting from blocking TGF-β1/Smad signaling, as well as increased the apoptosis of HSCs. The results suggest that casticin has potential benefits in the attenuation and treatment of liver fibrosis.
研究领域:
药理学
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肝病学
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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
PHARMACEUTICAL BIOLOGY
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2022
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IF 3.889
Hui Wang,Qingtao Jiang,Lizhu Zhang
Context Baicalin, a flavonoid extracted from radix scutellariae, possesses various pharmacological effects, including protective effects on renal interstitial fibrosis (RIF), but its possible role and mechanisms have not been fully elucidated.Objective This study explores the protective effects and mechanisms of baicalin on RIF.Materials and methods C57BL/6 male mice were divided into six groups: sham, model, low baicalin, middle baicalin, high baicalin and positive drug groups. The unilateral ureteral obstruction (UUO) model of RIF was constructed and treated with baicalin doses (10, 20 and 40 mg/kg) and a positive control drug (valsartan, 8 mg/kg). H&E staining was used to observe the pathological changes in renal tissues, Masson staining was performed to evaluate collagen deposition in renal tissues, and immunohistochemical examination was adopted to determine α-SMA and extracellular matrix (ECM) expression. Primary mouse fibroblasts were isolated, extracted and treated with baicalin and/or TGF-β. qRT-PCR and enzyme-linked immunosorbent assay (ELISA) were applied to detect the inflammatory responses. Moreover, ECM and TGF-β/Smad expression levels were evaluated by western blot assay.Results Baicalin ameliorated RIF in UUO mice by inhibiting fibrosis and inflammatory responses. The TGF-β/Smad pathway was significantly suppressed in the UUO mouse model. Additionally, baicalin significantly inhibited ECM expression and inflammatory factors in fibroblasts treated with TGF-β. TGF-β/Smad pathway activation was significantly decreased in fibroblasts.Discussion and conclusions These findings support the use of baicalin as a potential therapeutic option for the treatment of RIF by possibly inhibiting the TGF-β/Smad signalling pathway.
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
Chinese Herbal Medicines
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2026
·
IF 11.2
Aifen Liu,Jingyan Hu,Weili Yu,Chuanyu Cang,Chuanjing Shi,Xi Wang,Rui Wang,Xuanwei Cai,Fengbo Zhao,Lei Zhang
Objective Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder characterized by ovulatory dysfunction. Formononetin (FMN), a bioactive compound derived from leguminous plants, including Glycyrrhiza uralensis , Trifolium pratense , and Astragalus membranaceus , exhibits anti-inflammatory and anti-fibrotic properties. This study aimed to evaluate the therapeutic effects of FMN in a PCOS rat model and elucidate its underlying molecular mechanisms. Methods A PCOS-like model was established in 3-week-old female Sprague-Dawley rats by daily dehydroepiandrosterone (DHEA) injections. The efficacy of FMN was assessed by monitoring estrous cycles, hormone levels, glucose tolerance, and ovarian tissue morphology. Network pharmacology and transcriptome sequencing were used to predict the molecular targets and signaling pathways of FMN. The binding and stabilizing effects of FMN on suppressor of cytokine signaling 3 (SOCS3) were confirmed using molecular docking, molecular dynamics (MD) simulations, and cellular thermal shift assay (CETSA)-Western blotting (WB) (CETSA-WB). The expression of SOCS3, inflammation- and fibrosis-related markers, and the components of the transforming growth factor beta1 (TGF- β 1)/Smad pathway were quantified by quantitative polymerase chain reaction (qPCR), Western blotting, and immunohistochemistry. Functional validation was performed using SOCS3 small interfering RNA (siRNA). Results DHEA successfully induced a PCOS-like phenotype, including disrupted estrous cycle, hyperandrogenism, an elevated luteinizing hormone to follicular stimulating hormone (LH/FSH) ratio, insulin resistance, and abnormal ovarian morphology. FMN treatment significantly reversed these abnormalities and reduced ovarian collagen deposition. Network pharmacology and transcriptome analyses indicated that the therapeutic efficacy of FMN was primarily attributable to its anti-fibrotic and anti-inflammatory properties, with SOCS3 identified as a potential key molecule. Molecular docking and MD simulations, along with CETSA-WB, further revealed that FMN directly binds to SOCS3, enhancing its stability and thereby inhibiting ovarian fibrosis in PCOS. Moreover, qPCR, Western blotting, and immunohistochemistry confirmed that FMN regulates the TGF- β 1/Smad signaling pathway. Importantly, SOCS3siRNA abolished fibrotic-related collagen levels and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) expression, supporting the notion that FMN ameliorates PCOS-induced ovarian fibrosis via SOCS3. Conclusion FMN alleviated ovarian dysfunction and hyperandrogenism in DHEA-induced PCOS rats by stabilizing SOCS3 and inhibiting TGF- β 1/Smad signaling, thereby attenuating ovarian fibrosis and inflammation. This reveals a novel SOCS3-centered mechanism for FMN and underscores its therapeutic potential for PCOS.
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高影响因子
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