BMC Pulmonary Medicine
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2025
·Vol. 25
·期 1
·1-13
·
IF 2.8
Huang Zhiheng,Li Liangxian,Zhang Bingxi,Yao Dong,Xiao Bo,Mo Biwen
Background Bronchial asthma, a chronic inflammatory airway disease, is characterized by airway remodeling, including thickening of the airway smooth muscle layer, primarily due to abnormal proliferation of airway smooth muscle cells (ASMCs). CBL0137 (Curaxin-137 hydrochloride), a histone chaperone facilitate chromatin transcription (FACT) inhibitor, has demonstrated anti-tumor properties, including inhibition of proliferation, promotion of apoptosis, and increased autophagy. However, its effects on ASMCs and airway remodeling remain unexplored. Methods Asthma models were established using ovalbumin (OVA) in female C57BL/6 J mice, with therapeutic interventions using CBL0137 and budesonide. Lung tissues were analyzed using Hematoxylin and eosin (H&E), PAS, Masson’s trichrome, and α-SMA immunofluorescence staining. ASMCs extracted from Sprague–Dawley rats were cultured in vitro experiments, with phenotypic changes assessed via flow cytometry. Gene and protein expressions were analyzed using RT-PCR and Western blotting. Results CBL0137 significantly reduced airway resistance, goblet cell proliferation, alveolar collagen deposition, and airway smooth muscle layer thickening in asthmatic mice. In vitro, CBL0137 inhibited ASMC proliferation and induced apoptosis, downregulating cyclin-B1, Cdc2, and Bcl-2 while upregulating caspase-3. Conclusions CBL0137 mitigates airway remodeling of asthmatic mice by modulating ASMC proliferation and apoptosis, presenting a potential therapeutic strategy for asthma treatment.
研究领域:
药理学
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呼吸病学
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分子生物学
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DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2015
·Vol. 12
·期 5
·6656-6662
·
IF 1.554
Chengfei Zheng,Hui Niu,Ming Li,Hongkun Zhang,Zhenggang Yang,Lu Tian,Ziheng Wu,Donglin Li,Xudong Chen
Aortic aneurysm is a cardiovascular condition with a serious risk of mortality and the dismal prognosis of any type of major cardiovascular disease. The present study found that tissues from aortic aneurysm patients and hypoxic aortic smooth muscle cells showed aberrant high expression of the cyclic RNA hsa‑circ‑000595, as demonstrated by polymerase chain reaction array screening. Knockdown of hsa‑circ‑000595 resulted in a decreased apoptotic rate of human aortic smooth muscle cells. Furthermore, it was determined that miR‑19a is a target of hsa‑circ‑000595. The results of the present study laid an epigenetic foundation for exploring the underlying mechanisms of the development of aortic aneurysm.
研究领域:
心血管疾病
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分子生物学
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表观遗传学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2022
·
IF 5.195
Lin Niu,Jie Wang,Fukui Shen,Jie Gao,Min Jiang,Gang Bai
Ethnopharmacological relevance Magnolia officinalis Cortex ( M. officinalis ) is a classical traditional Chinese medicine (TCM) widely used to treat digestive system diseases . It effectively regulates gastrointestinal motility to improve abdominal pain, abdominal distension and other symptoms. Magnolol (MAG) and honokiol (HON) are the main pharmacodynamic components responsible for the gastrointestinal activity of M. officinalis . Aim of the study The transient receptor potential (TRP) family is highly expressed in the gastrointestinal tract and participates in the regulation of gastrointestinal motility, visceral hypersensitivity, visceral secretion and other physiological activities. In this study, the calcium-lowering mechanisms of MAG and HON contributing to the smooth muscle relaxation associated with TRP are discussed. Materials and methods The relaxation smooth muscle effects of MAG and HON were tested by the isolated intestine tone tests. A synthetic MAG probe (MAG-P) was used to target fishing for their possible target. The distribution of MAG on the smooth muscle was identified by a molecular tracer based on chemical biology. Ca 2+ imaging and dual-luciferase reporter assays were used to determine the effects on the target proteins. Finally, the calcium-mediating effects of MAG and HON on smooth muscle cells and TRPC4-knockdown cells were compared to verify the potential mechanism. Results After confirming the smooth muscle relaxation in the small intestine induced by MAG and HON, the relaxation effect was identified mainly due to the downregulation of intracellular calcium by controlling external calcium influx. Although MAG and HON inhibited both TRPV4 and TRPC4 channels to reduce calcium levels, the inhibitory effect on TRPC4 channels is an important mechanism of their smooth muscle relaxation effect, since TRPC4 is widely expressed in the small intestinal smooth muscle cells. Conclusions The inhibition of MAG and HON on TRPC4 channels contributes to the relaxation of intestinal smooth muscle.
研究领域:
药理学
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胃肠病学
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传统中药
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
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IF 5.6
Yu Shi,Yi Zhao,Si-Jia Sun,Xiu-Ting Lan,Wen-Bin Wu,Zhen Zhang,Yu-Xin Chen,Yu-Ying Yan,Yu-Ping Xu,Dong-Jie Li,Hui Fu,Fu-Ming Shen
Abdominal aortic aneurysm (AAA) is a potentially fatal cardiovascular disease, closely related to inflammation and loss of vascular smooth muscle cells (VSMCs). Ferroptosis is an iron-dependent cell death associated with peroxidation of lipids. However, the direct role of glutathione peroxidase 4 (GPX4) itself determined ferroptosis in the course of AAA pathogenesis remains unknown. Here, we reported that ferroptosis was triggered in human AAA, elastase- and angiotensin II (Ang II)-induced mouse AAA, and Ang II-incubated VSMCs. Inhibition of ferroptosis via global genetic overexpression of GPX4, a critical anti-ferroptosis molecule, markedly prevented both vascular remodeling and inflammatory response. Mechanistically, GPX4 changed the migration and activation of macrophages/monocytes in AAA tissues in mice. Experiments in vitro demonstrated that overexpression of GPX4 prevented the JAK1/STAT3 signaling activation in VSMCs induced by IL-6, production of pro-inflammatory macrophages. Finally, the role of ferroptosis was confirmed on an Ang II-induced mice AAA model. These results emphasized the significance of ferroptosis in AAA, and provided novel insights that therapy focusing on GPX4 might be a promising strategy for treatment of AAA in the clinic.
研究领域:
心血管疾病
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR MEDICINE-JMM
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2025
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IF 4.2
Wen Xin,Peng Yuefeng,Yang Wenqing,Zhu Yuzhong,Yu Fan,Geng Li,Wang Xianfeng,Wang Xiaoyan,Zhang Xiaodong,Tang Yi,Feng Lei,Zhou Tingting,Jia Hongliang,Yang Liu
Transient receptor potential canonical 1 (TRPC1) channel, a Ca 2+ -permeable ion channel widely expressed in vasculature, has been reported to be involved in various cardiovascular disorders. However, the pathophysiological function of vascular smooth muscle cell (VSMC)-derived TRPC1 in hypertension and hypertensive cardiovascular remodeling remains to be defined. In this study, we found increased TRPC1 expression in both angiotensin II (AngII)-treated VSMCs and aortas from AngII-infused mice. VSMC-specific TRPC1 deficiency strikingly attenuated AngII-induced vasoconstriction, hypertension, vascular remodeling, and cardiac hypertrophy. Mechanistically, AngII activated enhancer of zeste homolog 2 (EZH2) to stimulate TRPC1 expression, induced calcium influx and phosphorylation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK-ERK), which in turn triggered VSMC proliferation and migration and exacerbated hypertension and cardiovascular remodeling. Treatment with EZH2 inhibitor reduced VSMC proliferation and migration and alleviated vasoconstriction and hypertension in AngII-infused mice. Together, we revealed the pathogenic role of the EZH2-TRPC1-MEK/ERK pathway in AngII-induced hypertension and cardiovascular damage. TRPC1 or EZH2 inhibition may represent a desirable therapeutic target for the treatment of hypertension. Key messages
AngII activates AT1R-EZH2-TRPC1 pathway in VSMCs and aortas of hypertensive mice.
TRPC1 promotes VSMC proliferation and migration via MEK/ERK signaling.
Inhibition of TRPC1 or EZH2 alleviates hypertension and cardiovascular remodeling.
研究领域:
心血管病学
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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
EUROPEAN JOURNAL OF PHARMACOLOGY
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2025
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IF 4.7
Meizhu Wu,Yuting Zhou,Zhi Guo,Dawei Lian,Hong Chen,Renfeng Li,Jing Lin,Farman Ali,Aling Shen,Jun Peng
Isoliensinine, a bioactive alkaloid derived from Nelumbo nucifera Gaertn , has antihypertension effects. This study investigated its antihypertensive effect and molecular mechanism. Spontaneously hypertensive rats (SHRs) and Wistar Kyoto rats (n=6 per group) were treated with 2.5, 5 or 10 mg/kg isoliensinine or 7 mg/kg valsartan for 10 weeks. Ultrasonography, histology, immunohistochemistry, RNA-sequencing analysis, vascular tension, calcium imaging, and virtual docking were performed. Isoliensinine effectively attenuated the elevation of blood pressure, pulse wave velocity, and medial thickness of the abdominal aortas in SHRs. It reversed 253-upregulated and 161-downregulated differentially expressed transcripts in the abdominal aorta of SHRs, with enrichment in vascular smooth muscle contraction and calcium signaling pathways. Isoliensinine significantly attenuated the vasoconstriction induced by angiotensin II (Ang II), norepinephrine (NE), or potassium chloride (KCl) and maintained its inhibitory effects across increasing calcium concentrations. It promotes vasodilation in the abdominal aorta rings induced by NE or KCl independent of the endothelium and potassium ion channels but is associated with the modulation of L-type calcium channels. Isoliensinine also suppressed calcium release in vascular smooth muscle cells after KCl, Ang II, or NE stimulation. Isoliensinine upregulated the expression of MLCP but downregulated that of p-MLC2 in the abdominal aorta of SHRs. Virtual docking analysis revealed lower binding energy values for isoliensinine with MLCP, suggesting a potential interaction. Isoliensinine lowers blood pressure by regulating vascular smooth muscle contraction and relaxation, and its effects are potentially mediated by regulating calcium signaling pathways.
研究领域:
药理学
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心血管生物学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
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2025
·
IF 16
Jiayi Zhang,Yang Li,Zhen Xiang,Hongxia Pu,Cheng Ji,Xingrong Ren,Daihua Fu,Yunbing Wang
Stent implantation remains a cornerstone of interventional cardiology, providing a minimally invasive solution to restore blood flow in occluded vessels. However, current stents face persistent challenges in simultaneously preventing neointimal hyperplasia and promoting reendothelialization, compromising their long-term efficacy. To address these limitations, we developed an in situ H2S-releasing polymer brush-coated stent that actively modulates material–blood interactions, creating a favorable microenvironment for vascular healing. H2S enhances the stent’s antithrombotic properties by inhibiting fibrinogen binding and platelet activation, while also mitigating oxidative stress and promoting macrophage polarization toward the anti-inflammatory M2 phenotype. In vivo, the H2S-releasing stents significantly improved vascular healing by accelerating endothelialization and inhibiting smooth muscle cell overproliferation, resulting in a thinner neointima with functional endothelial coverage. Transcriptomic analysis further elucidated the underlying mechanisms, revealing H2S-mediated modulation of key biological pathways that support vascular healing. These findings underscore the potential of in situ H2S release as an effective strategy for optimizing vascular implants and improving long-term outcomes.
研究领域:
心血管医学
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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
Gastroenterology Research and Practice
·
2020
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IF 1.806
Guo-xiang Wang,Yan-li Xiang,Hong-gang Wang,Yang-de Miu,Guang Yu
Evodiamine (Evo) is an indole alkaloid extracted from the traditional Chinese medicinal herb Evodia rutaecarpa. Evo may regulate gastrointestinal motility, but the evidence is insufficient, and the mechanisms remain unknown. The aim of this study was to investigate the effect of Evo on colonic motility of rats and the underlying mechanisms in vitro. Rat colonic muscle was exposed to Evo (10 and 100 μM) followed by immunohistochemistry of cholecystokinin receptor 1 (CCK1R). Muscle contractions were studied in an organ bath system to determine whether CCK1R, nitric oxide (NO), and enteric neurons are involved in the relaxant effect of Evo. Whole-cell patch-clamp was used to detect L-type calcium currents () in isolated colonic smooth muscle cells (SMCs). CCK1R was observed in SMCs, intermuscular neurons, and mucosa of rat colon. Evo could inhibit spontaneous muscle contractions; NO synthase, inhibitor L-NAME CCK1R antagonist, could partly block this effect, while the enteric neurons may not play a major role. Evo inhibited the peak in colonic SMCs at a membrane potential of 0 mV. The current-voltage (I–V) relationship of L-type calcium channels was modified by Evo, while the peak of the I–V curve remained at 0 mV. Furthermore, Evo inhibited the activation of L-type calcium channels and decreased the peak . The relaxant effect of Evo on colonic muscle is associated with the inhibition of L-type calcium channels. The enteric neurons, NO, and CCK1R may be partly related to the inhibitory effect of Evo on colonic motility. This study provides the first evidence that evodiamine can regulate colonic motility in rats by mediating calcium homeostasis in smooth muscle cells. These data form a theoretical basis for the clinical application of evodiamine for treatment of gastrointestinal motility diseases.
研究领域:
药理学
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生理学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
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IF 8.3
Feng Jia,Yongqing Wang,Zhiqiang Chen,Jingxian Jin,Lei Zeng,Li Zhang,Huaijian Tang,Yanyan Wang,Pei Fan
Background 10-Hydroxydec-2-enoic acid (10-HDA), a unique and marker compound in royal jelly, has a wide range of bio-activities. However, its role in regulating inflammation of vascular smooth muscle cell (VSMC), which is essential to a set of vascular diseases, is still unknown. Purpose Our study aimed to investigate whether 10-HDA exerts effect on VSMC inflammation via interacting with toll-like receptor 4 (TLR4), a pivotal inflammatory initiator. Methods A package of proteins, which might participate in TLR4-mediated signaling, influenced by 10-HDA were analyzed in mouse VSMCs with Angiotensin Ⅱ(Ang Ⅱ) or lipopolysaccharide (LPS) stimulation. Accordingly, pro- or anti-inflammatory cytokines, reactive oxygen species (ROS), and anti-oxidants that are closely relevant to inflammatory process were determined. The possible mode for 10-HDA interacting with TLR4 was also characterized. Moreover, involvement of a key miRNA in 10-HDA regulating VSMC inflammation was identified. Results In the presence of Ang Ⅱ, 10-HDA inhibited the TLR4 expression in a dose-dependent manner. In such occasion, 10-HDA hindered the up-regulation of specificity protein 1 (SP1) and serine/threonine-protein phosphatase 6 catalytic subunit (PPP6C), the phosphorylation of extracellular signal-regulated kinase 1/2, TGF-β-activated kinase 1, and nuclear factor-κB p56, as well as the enhancement of myeloid differentiation primary response gene 88. Apart from SP1 and PPP6C, the level change of these proteins by 10-HDA was similar with LPS stimulation. The effect might be resulted from 10-HDA blocking TLR4 through multiple atomic interactions. 10-HDA mitigated the increase of pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin-2 (IL-2), and IL-6, as well as increased the anti-inflammatory cytokine IL-10, in the Ang Ⅱ- or LPS-induced VSMCs. Correspondingly, the level of ROS was attenuated and the anti-oxidants such as glutathione and superoxide dismutase were fortified. The data indicated the anti-inflammatory potential of 10-HDA in VSMCs, which was associated with 10-HDA's capability of relieving oxidative stress. Additionally, the expression of miR-17–5p was saved by 10-HDA from Ang Ⅱ- or LPS-treated VSMCs, which might be relevant to SP1 and PPP6C targeting. Conclusion The present work of 10-HDA, for the first time, revealed its ability to alleviate VSMC inflammation by targeting TLR4 and therefore modulate the downstream inflammatory participants. Our data will cast light on the utilization of 10-HDA in VSMC inflammation-related vascular disorders.
研究领域:
药理学
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分子生物学
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心血管疾病
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产品关联
DOI
PubMed
高影响因子
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
·
2014
·Vol. 47
·期 12
·1068-1074
·
IF 1.034
Yao Q.Y.,Chen D.P.,Ye D.M.,Diao Y.P.,Lin Y.
Taurine (2-aminoethanesulfonic acid) is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM) can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca2+dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism.
研究领域:
药理学
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消化系统生理学
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DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
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2022
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IF 7.31
Lili Shi,Yuliang Li,Meixin Shi,Xiaoxue Li,Guopeng Li,Jie Cen,Dan Liu,Can Wei,Yan Lin
Background. It is well-known that dysfunctions of vascular smooth muscle cells (VSMCs) act an essential part in vascular complications of diabetes. Studies have shown that circular RNAs (circRNAs) and microRNAs (miRNAs) play a crucial role in regulating cell functions. However, their influence on the proliferation, calcification, and autophagy of VSMCs remains to be further explored. Therefore, this study elucidates the role and mechanism of hsa_circRNA_0008028 in high glucose- (HG-, 30 mM) treated VSMCs in vitro. Methods. Quantitative real-time polymerase chain reaction (qRT-PCR) was chosen to detect the levels of hsa_circRNA_0008028, miR-182-5p, and tribble 3 (TRIB3). Then, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to predict and verify the binding relationship between miR-182-5p and hsa_circRNA_0008028 or TRIB3. Cell counting kit-8 assay, 5-ethynyl-2-deoxyuridine (EdU) staining, corresponding commercial kits, and western blotting were used to measure indexes reflecting cell viability, proliferation, calcification, and autophagy of VSMCs, respectively. Results. In HG-induced VSMCs, hsa_circRNA_0008028 and TRIB3 were highly expressed, whereas miR-182-5p decreased. Meanwhile, cell proliferation, calcification, and autophagy could be repressed by silencing of hsa_circRNA_0008028. However, these effects can be eliminated by miR-182-5p inhibition. Furthermore, it was demonstrated that hsa_circRNA_0008028 could promote the expression of TRIB3, a target of miR-182-5p, by directly sponging miR-182-5p. The expression of TRIB3 was suppressed by hsa_circRNA_0008028 knockout, which was rescued by miR-182-5p inhibition. Conclusion. This study reveals that hsa_circRNA_0008028 can act as a sponge of miR-182-5p and promote HG-induced proliferation, calcification, and autophagy of VSMCs partly by regulating TRIB3.
研究领域:
分子生物学
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细胞生物学
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糖尿病研究
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
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IF 14.1
Yanjun Liu,Jianxujie Zheng,Lingyan Zhong,Zengyu Wang,Dan Zhao,Hong Lin,Xiaoxue Zhang,Ke Meng,Xiaoxia Yang,Dongxue Zhang,Ling Lin,Liang Qiao
Hypertension, the leading cause of cardiovascular disease and premature mortality, is characterized by increased vessel stretch and alterations in vascular smooth muscle cells (VSMCs). In this study, a vessel-on-a-chip model is developed to simulate both physiological and pathological stretch conditions alongside a mouse model of hypertension. Proteomics analysis is applied to investigate changes in VSMCs using the vessel-on-a-chip system and compared these findings with data from the mouse model. The results demonstrates that physiological stretch enhances the expression of contractile markers in VSMCs. Additionally, the chip effectively replicates cellular responses to pathological stretch and stress, including the upregulation of ERK signaling, calcium ion transport pathway, integrin signaling pathway, endoplasmic reticulum stress, toll-like receptor activation, oxidative stress, and synthesis of sphingolipids and ceramides. These findings indicate that the vessel chip successfully mimics in vivo biological events associated with hypertension. The vessel-on-a-chip system holds promise for advancing the study of vessel-related diseases and facilitating the development of novel hypertension therapeutics.
研究领域:
生物医学工程
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心血管科学
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分子生物学
✓ 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）