General physiology and biophysics最新文献_第3页

PAG1 aggravates diabetic nephropathy through TGF-β1/Smads-driven pyroptosis. PAG1通过TGF-β1/ smads驱动的焦亡加重糖尿病肾病。

IF 1.5 4区生物学

General physiology and biophysics Pub Date : 2026-05-01 DOI: 10.4149/gpb_2026006

Xue Han, Chen Xie, Song Xue

{"title":"PAG1 aggravates diabetic nephropathy through TGF-β1/Smads-driven pyroptosis.","authors":"Xue Han, Chen Xie, Song Xue","doi":"10.4149/gpb_2026006","DOIUrl":"https://doi.org/10.4149/gpb_2026006","url":null,"abstract":"Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1) has been recognized as a biomarker for diabetic nephropathy (DN). This study aimed to elucidate the mechanism by which PAG1 influences DN. The expression and clinical significance of PAG1 in DN were assessed using bioinformatics analysis. PAG1 expression was validated in db/db mice and high glucose (HG)-treated human kidney-2 (HK-2) cells. Subsequently, PAG1 was knocked down in DN models to investigate its effects on DN progression, pyroptosis, and the transforming growth factorbeta 1 (TGF-β1)/Smads pathway. The TGF-β1/Smads pathway activator SRI-011381 was employed to further elucidate the role of PAG1 in DN regulation. Bioinformatics analysis revealed elevated PAG1 expression in DN samples, which correlated with various immune cells and pathways, such as chemokine pathway and cell cycle. This elevated expression was confirmed in animal and cell experiments. In db/db mice, PAG1 knockdown alleviated DN, reduced inflammatory factor levels, inhibited pyroptosis, and suppressed TGF-β1/Smads pathway. In vitro, PAG1 silencing promoted proliferation, inhibited apoptosis and fibrosis, reduced inflammatory and pyroptotic factor levels, and suppressed the TGF-β1/Smads pathway. These effects were reversed by SRI-011381 intervention. PAG1 promotes pyroptosis by upregulating the TGF-β1/Smads pathway, thereby exacerbating DN.","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":"45 3","pages":"245-257"},"PeriodicalIF":1.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148264090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Silencing miR-208a-3p promotes autophagy and attenuates high glucose-triggered podocyte injury by activating VAV3/AKT/mTOR pathway. 沉默miR-208a-3p可通过激活VAV3/AKT/mTOR通路促进自噬并减轻高糖触发的足细胞损伤。

IF 1.5 4区生物学

General physiology and biophysics Pub Date : 2026-05-01 DOI: 10.4149/gpb_2026008

Mengjie Wang, Zhen Chen, Rui Ma, Yongdong Ren, Hairui Chen, Li Li, Xiaoyu Lv, Xuyan Zhang, Zhongjing Wang, Jing Li

{"title":"Silencing miR-208a-3p promotes autophagy and attenuates high glucose-triggered podocyte injury by activating VAV3/AKT/mTOR pathway.","authors":"Mengjie Wang, Zhen Chen, Rui Ma, Yongdong Ren, Hairui Chen, Li Li, Xiaoyu Lv, Xuyan Zhang, Zhongjing Wang, Jing Li","doi":"10.4149/gpb_2026008","DOIUrl":"https://doi.org/10.4149/gpb_2026008","url":null,"abstract":"Dysregulation of microRNAs (miRNAs) has been associated with podocyte injury in diabetic nephropathy (DN). This study aimed to investigate the role and underlying mechanism of miR-208a-3p in the development of DN. An in vitro DN model was established by treating podocytes with high glucose (HG). Gene expression was analyzed using reverse transcription quantitative polymerase chain reaction, and protein levels were determined by Western blotting. Immunofluorescence staining was performed to assess microtubule-associated protein 1A/1B-light chain 3 (LC3) intensity as an autophagy marker. Podocyte viability and apoptosis were evaluated via Cell Counting Kit-8 assay and flow cytometry, respectively. Intracellular reactive oxygen species (ROS) levels were measured using 2',7'-dichlorofluorescin diacetate staining. miR-208a-3p was significantly upregulated in HG-stimulated podocytes. HG exposure promoted apoptosis and oxidative stress, while suppressing autophagy and cell viability, effects that were reversed by miR-208a-3p inhibition. Mechanistically, miR-208a-3p directly targeted vav guanine nucleotide exchange factor 3 (VAV3). HG suppressed AKT/mTOR signaling, whereas miR-208a-3p silencing activated it. Conversely, VAV3 knockdown inactivated AKT/mTOR signaling. VAV3 downregulation or treatment with LY294002, an AKT/mTOR inhibitor, abolished the protective effects of miR-208a-3p silencing against HG-induced podocyte injury. These findings indicate that miR-208a-3p silencing attenuates HG-induced podocyte injury by promoting autophagy via targeting the VAV3/AKT/mTOR pathway.","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":"45 3","pages":"297-309"},"PeriodicalIF":1.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148264085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cyanidin-3-O-arabinoside improves high-fat diet-induced glucose and lipid metabolism disorder in mice by restoring fatty acid oxidation and mitochondrial function through CD36/AMPK/PGC-1α. 花青素-3- o -阿拉伯糖苷通过CD36/AMPK/PGC-1α恢复脂肪酸氧化和线粒体功能，改善高脂肪饮食诱导的小鼠糖脂代谢紊乱。

IF 1.5 4区生物学

General physiology and biophysics Pub Date : 2026-05-01 DOI: 10.4149/gpb_2026007

Rong Li, Zhaoyin Zhong, Haifeng Lu, Dongmei Wang, Changyi Wu

{"title":"Cyanidin-3-O-arabinoside improves high-fat diet-induced glucose and lipid metabolism disorder in mice by restoring fatty acid oxidation and mitochondrial function through CD36/AMPK/PGC-1α.","authors":"Rong Li, Zhaoyin Zhong, Haifeng Lu, Dongmei Wang, Changyi Wu","doi":"10.4149/gpb_2026007","DOIUrl":"https://doi.org/10.4149/gpb_2026007","url":null,"abstract":"The peel of Malus doumeri (Big Fruit Hawthorn) is rich in Cyanidin-3-O-arabinoside (C3A), which can attenuate weight gain and adipogenic pathways in obese mice. The mice were treated with a high-fat diet (HFD) to induce glucose and lipid metabolism disorder (GLMD). After 8 weeks, the mice were treated with C3A, and CD36 was highly expressed by AAV8-TBG. The blood glucose, blood lipid, and liver injury status were evaluated. Liver steatosis and fatty acid oxidation (FAO) were detected by pathological staining and Western blot. Transmission electron microscopy and kits detected mitochondrial function, and the CD36/AMPK/PGC-1α proteins were detected. C3A significantly reduced fasting blood glucose (FBG), TC, and ALT levels, and significantly reduced hepatocyte steatosis and oil red O-stained lipid droplets. The FAO-related proteins were promoted, and the number of mitochondria, ATP content, and OXPHOS level were significantly increased. C3A affected the expression of CD36 to regulate the AMPK/PGC-1α axis. However, after CD36 overexpression, abnormal glucose and lipid metabolism, FAO damage, and mitochondrial function damage in mice weakened the improvement effect of C3A on GLMD. C3A activated the CD36/AMPK/PGC-1α pathway to improve HFD-induced FAO damage and mitochondrial dysfunction, thereby protecting glucose and lipid metabolism in mice.","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":"45 3","pages":"269-286"},"PeriodicalIF":1.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148264034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association between the expression levels of miR-17-5p/IGFBP5 and exercise-induced physiological cardiac hypertrophy. miR-17-5p/IGFBP5表达水平与运动诱导的生理性心肌肥厚的关系

IF 1.5 4区生物学

General physiology and biophysics Pub Date : 2026-05-01 DOI: 10.4149/gpb_2026002

Yao-Zong Guan, Huai Wang, Huan-Jie Huang, Dong-Yan Liang, Hao Liu

{"title":"Association between the expression levels of miR-17-5p/IGFBP5 and exercise-induced physiological cardiac hypertrophy.","authors":"Yao-Zong Guan, Huai Wang, Huan-Jie Huang, Dong-Yan Liang, Hao Liu","doi":"10.4149/gpb_2026002","DOIUrl":"https://doi.org/10.4149/gpb_2026002","url":null,"abstract":"Pathological cardiac hypertrophy (PaCH) leads to heart failure, whereas exercise-induced physiological cardiac hypertrophy (PhCH) represents a benign adaptive response, and counteracts PaCH. Here, we investigated the association of miR-17-5p and IGFBP5 expressions with PhCH through a PhCH group (five mice with 21-days swimming exercise) and healthy controls (n = 5). The PhCH group showed higher body weight (BW), heart weight (HW), HW/BW ratio, ventricular septal thickness, left-ventricular end-diastolic diameter, and left-ventricular end-systolic diameter than control group (p < 0.05 for all). The IGFBP5 expression was significantly reduced, whereas miR-17-5p expression was significantly elevated in PhCH group (p < 0.05). Dual-luciferase assays validated the direct binding of miR-17-5p with IGFBP5. Wheat germ agglutinin staining revealed enlarged cardiomyocytes of PhCH group, while Masson staining disclosed no increase of fibrosis. The reduction of IGFBP5 and elevation of miR-17-5p are associated with PhCH, suggesting their potentials for further researches in myocardial hypertrophy.","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":"45 3","pages":"287-296"},"PeriodicalIF":1.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148264050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lipid emulsion attenuates theophylline-induced cardiotoxicity in rat cardiomyoblasts. 脂质乳剂减轻茶碱诱导的大鼠成心肌细胞心脏毒性。

IF 1.5 4区生物学

General physiology and biophysics Pub Date : 2026-05-01 DOI: 10.4149/gpb_2026003

Soo Hee Lee, Seung Hyun Ahn, Seong-Ho Ok, Gyujin Sim, Kyeong-Eon Park, Seunghyeon Park, Ju-Tae Sohn

{"title":"Lipid emulsion attenuates theophylline-induced cardiotoxicity in rat cardiomyoblasts.","authors":"Soo Hee Lee, Seung Hyun Ahn, Seong-Ho Ok, Gyujin Sim, Kyeong-Eon Park, Seunghyeon Park, Ju-Tae Sohn","doi":"10.4149/gpb_2026003","DOIUrl":"https://doi.org/10.4149/gpb_2026003","url":null,"abstract":"Theophylline, a bronchodilator, induces cardiotoxicity due to its narrow therapeutic index. Lipid emulsion is used as a nonspecific antidote. However, its effects on theophylline-induced cardiotoxicity remain unknown. This study aimed to examine the effects of lipid emulsion on cardiotoxicity induced by toxic doses of theophylline in H9c2 rat cardiomyoblasts. The effects of theophylline and lipid emulsion (Lipofundin MCT/LCT), alone or in combination, on cell viability and migration were examined. Moreover, their effects on cleaved caspase-3, Bax/Bcl-XL ratio, and cleaved caspase-9 and caspase-8 expression, nuclear factor-κβ (NF-κβ) phosphorylation, and TUNEL-positive cells were examined. Theophylline treatment decreased cell viability. Lipofundin MCT/LCT (0.1-1%) with 50% longchain and 50% medium-chain fatty acids inhibited the theophylline-induced reduction in cell viability (3×10-3 M). It partially inhibited the theophylline-induced decrease in cell migration. Further, it reversed the theophylline-induced increase in cleaved caspase-3, Bax/Bcl-XL ratio, and cleaved caspase-9 expression as well as NF-κβ (Ser536) phosphorylation. However, theophylline treatment did not alter cleaved caspase-8 expression. Additionally, lipid emulsion inhibited theophylline-induced increase in TUNELpositive cells. Taken together, these results suggest that lipid emulsion reverses theophylline-induced apoptosis in cardiomyoblasts via inhibition of the mitochondrial apoptotic pathway associated with NF-κβ (Ser536) phosphorylation, indicating its potential for treating theophylline-induced cardiotoxicity.","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":"45 3","pages":"311-320"},"PeriodicalIF":1.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148264017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Carvotanacetone from Saposhnikoviae radix restores skin barrier by regulating SP1 and Claudin-1. 藿香卡伏酮通过调节SP1和Claudin-1修复皮肤屏障。

IF 1.5 4区生物学

General physiology and biophysics Pub Date : 2026-05-01 DOI: 10.4149/gpb_2026005

Liying Jia, Weihong Ying, Gairong Liu, Peng Yang, Yizhi Zheng

引用次数: 0

PCSK9 inhibitor Evolocumab alleviates atherosclerosis progression by suppressing endothelial cell injury via the ROS/MAPK pathway. PCSK9抑制剂Evolocumab通过ROS/MAPK途径抑制内皮细胞损伤，从而缓解动脉粥样硬化进展。

IF 1.3 4区生物学

General physiology and biophysics Pub Date : 2026-03-01 DOI: 10.4149/gpb_2025043

Menghuai Ma, Fan Liu, Xiaomei Yin, Jianhong Yue, Yanhua Duan, Jiong Tang

{"title":"PCSK9 inhibitor Evolocumab alleviates atherosclerosis progression by suppressing endothelial cell injury via the ROS/MAPK pathway.","authors":"Menghuai Ma, Fan Liu, Xiaomei Yin, Jianhong Yue, Yanhua Duan, Jiong Tang","doi":"10.4149/gpb_2025043","DOIUrl":"10.4149/gpb_2025043","url":null,"abstract":"Atherosclerosis (AS) progression is closely linked to oxidized low-density lipoprotein (Ox-LDL)-induced endothelial cell injury. This study investigates the molecular mechanism by which the PCSK9 inhibitor Evolocumab (EVC) alleviates AS. We used Ox-LDL-induced HUVECs and high-fat diet (HFD)-fed ApoE-/- mice as in vitro and in vivo AS models. AS plaque formation was detected by HE and Oil Red O staining. The levels of lipid indicators and oxidative stress-related factors were measured via ELISA. The expression levels of PCSK9, apoptosis-related proteins, and signaling pathway-related proteins were determined via Western blotting. The result shows that EVC improved blood lipids and alleviated aortic injury in atherosclerotic mice, and concomitantly suppressed Ox-LDL-induced apoptosis and oxidative stress in HUVECs. In terms of the molecular mechanism, EVC attenuated the Ox-LDL-induced phosphorylation of ERK1/2, JNK and p38. Both the ROS inhibitor N-acetylcysteine and the p38 MAPK signaling pathway inhibitor SB203580 can enhance the suppressive effect of the PCSK9 inhibitor EVC on Ox-LDL induced apoptosis and oxidative stress in HUVECs, while the p38 MAPK signaling pathway activator C16-PAF shows the opposite results. In conclusion, the PCSK9 inhibitor EVC inhibits Ox-LDL-induced HUVECs apoptosis and oxidative stress by inhibiting the ROS/MAPK signaling pathway, thereby alleviating the progression of AS.","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":"45 2","pages":"153-165"},"PeriodicalIF":1.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148224388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of gut microbiota in the neurobiology and treatment of Alzheimer's disease. 肠道微生物群在阿尔茨海默病的神经生物学和治疗中的作用。

IF 1.3 4区生物学

General physiology and biophysics Pub Date : 2026-03-01 DOI: 10.4149/gpb_2025042

Seyed Khalil Rashidi, Mitra Ansari Dezfouli, Hamidreza Khalili, Ali Kiani Deh Kiani

{"title":"The role of gut microbiota in the neurobiology and treatment of Alzheimer's disease.","authors":"Seyed Khalil Rashidi, Mitra Ansari Dezfouli, Hamidreza Khalili, Ali Kiani Deh Kiani","doi":"10.4149/gpb_2025042","DOIUrl":"10.4149/gpb_2025042","url":null,"abstract":"Alzheimer's disease (AD) is the most common cause of dementia in the elderly population and characterized by progressive cognitive decline. The major pathological features of AD are the accumulation of extracellular amyloid-beta protein as neuritic plaques and intracellular hyperphosphorylated tau protein as neurofibrillary tangles. Studies have shown that gut microbiota are involved in several central nervous system disorders through regulation of neurotransmitter production, blood-brain barrier permeability and immune responses. The gut microbiota establishes a two-way communication between the gut and the brain through neural, endocrine, and immune pathways, which play a role in various neurological diseases, including AD. Alterations in the composition and function of the gut microbiota may influence neuroinflammation, amyloid-beta accumulation, and tau pathology. Targeting the balance of the gut microbiota through probiotics, prebiotics, and fecal microbial transplantation could be promising therapeutic approach against neurodegeneration. Understanding the complex relationship between the gut microbiota and AD pathobiology could pave the way for novel preventive and therapeutic strategies. Here, we summarized advances in the role of gut microbiota in AD pathobiology and updated rising concerns from recent reports. Moreover, the possibility of applying the capability of the gut microbiota as a promising treatment against AD has been discussed in this review.","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":"45 2","pages":"129-151"},"PeriodicalIF":1.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148224472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

USP30 promotes cytarabine resistance in acute myeloid leukemia by deubiquitinating and stabilizing FOXM1. USP30通过去泛素化和稳定FOXM1促进急性髓系白血病的阿糖胞苷耐药。

IF 1.3 4区生物学

General physiology and biophysics Pub Date : 2026-03-01 DOI: 10.4149/gpb_2025046

Yaxuan Jiang, Zhen Zhang, Huilin Shu, Ronghua Li, Zhongcui Zhang, Ben Ma, Yan Wang

{"title":"USP30 promotes cytarabine resistance in acute myeloid leukemia by deubiquitinating and stabilizing FOXM1.","authors":"Yaxuan Jiang, Zhen Zhang, Huilin Shu, Ronghua Li, Zhongcui Zhang, Ben Ma, Yan Wang","doi":"10.4149/gpb_2025046","DOIUrl":"10.4149/gpb_2025046","url":null,"abstract":"Acute myeloid leukemia (AML) is a hematologic malignancy. Cytarabine (Ara-C) is a key drug in its chemotherapy, yet the development of drug resistance remains a major cause of treatment failure. Ubiquitin specific peptidase 30 (USP30) and forkhead box M1 (FOXM1) have been implicated in the progression of AML, yet the mutual regulatory mechanism between them remains unclear. Western blot was employed to assess the protein expression of USP30 and FOXM1 in tissues and cells. Cell proliferation and cell cycle were evaluated by EdU and flow cytometry assays. Cell apoptosis was determined using flow cytometry and TUNEL assays. The UbiBrowser 2.0, Co-IP, and cycloheximide (CHX) assays were applied to assess the interaction between USP30 and FOXM1. Subsequently, Ara-C-resistant cell lines and animal models were established, and immunohistochemistry (IHC) was performed to analyze Ki-67 and USP30 expression in tumor tissues from mice. The results showed that USP30 and FOXM1 were highly expressed in AML. Knockdown of USP30 repressed cell proliferation and cell cycle progression and promoted cell apoptosis. Additionally, USP30 stabilized FOXM1 protein expression through its deubiquitination activity. FOXM1 overexpression reversed the impacts of USP30 silencing on proliferation, cell cycle, and apoptosis in AML cells. Furthermore, USP30 enhanced Ara-C resistance in AML cells in vivo. Together, USP30 promoted Ara-C resistance in AML by deubiquitinating and stabilizing FOXM1, thereby enhancing tumor growth and cell survival.","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":"45 2","pages":"179-190"},"PeriodicalIF":1.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148224397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrated evaluation of genetic and pharmacological RAGE inhibition reveals a multidimensional therapeutic strategy for diabetic atherosclerosis. 综合评价基因和药理学抑制RAGE揭示了糖尿病动脉粥样硬化的多维治疗策略。

IF 1.3 4区生物学

General physiology and biophysics Pub Date : 2026-03-01 DOI: 10.4149/gpb_2025041

Yongcong He, Fan Wu, Jun Lai, Zebing Ye, Jijin Lin

{"title":"Integrated evaluation of genetic and pharmacological RAGE inhibition reveals a multidimensional therapeutic strategy for diabetic atherosclerosis.","authors":"Yongcong He, Fan Wu, Jun Lai, Zebing Ye, Jijin Lin","doi":"10.4149/gpb_2025041","DOIUrl":"10.4149/gpb_2025041","url":null,"abstract":"Atherosclerotic vascular disease is the major cause of mortality in type 2 diabetes. This study sought to examine the effects of different receptor for advanced glycation end-products (RAGE)-targeted interventions in diabetic atherosclerosis. A diabetic atherosclerosis model was constructed in ApoE-/- mice by high-fat diet feeding combined with streptozotocin injection. Human umbilical vein endothelial cells were treated with high glucose and oxidized low-density lipoprotein. RAGE was inhibited via three strategies: overexpression of soluble RAGE (sRAGE), small interfering RNA (siRNA) or short hairpin RNA (shRNA)-mediated knockdown of RAGE, and pharmacological blockade using FPS-ZM1. RAGE inhibition suppressed systemic and vascular inflammation. RAGE inhibition elevated endothelial nitric oxide synthase levels and downregulated vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 expression to improve endothelial dysfunction. RAGE blockade improved lipid metabolism, resulting in decreased total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels while elevating high-density lipoprotein cholesterol concentrations. These effects were confirmed in both in vivo and in vitro models. RAGE inhibition mitigated aortic structural damage and lipid deposition in diabetic atherosclerotic mice. These protective effects were consistently observed across all three intervention strategies. Genetic and pharmacological RAGE inhibition alleviates diabetic atherosclerosis and represents a potential therapeutic target for diabetes-related macrovascular complications.","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":"45 2","pages":"207-217"},"PeriodicalIF":1.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148224456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0