{"title":"LAMC1通过PI3K/AKT信号调节视网膜色素上皮细胞的上皮-间质转化，加重糖尿病视网膜病变。","authors":"Lei Liu, Yanlin Gao, Shiqi Yao","doi":"10.1016/j.jphyss.2025.100045","DOIUrl":null,"url":null,"abstract":"<p><p>Diabetic retinopathy (DR), a leading cause of adult blindness, with LAMC1-mediated epithelial-mesenchymal transition (EMT) playing a key role. By analyzing DR-related microarray datasets (GSE60436/GSE102485) from GEO, we identified 685 differentially expressed genes (570 downregulated, 115 upregulated). Functional and WGCNA analyses linked these to PI3K/Akt signaling, revealing 11 diagnostic hub genes, including LAMC1. Western blot analysis confirmed that LAMC1 significantly upregulated in high glucose (HG)-treated ARPE-19 cells and diabetic mouse retinas. In vitro and in vivo experiments confirmed that LAMC1 promotes EMT in retinal pigment epithelial (RPE) cells via PI3K/Akt activation, enhancing migration and invasion. Conversely, LAMC1 knockdown alleviated retinal damage in diabetic mice. Our studies uncovered that LAMC1's role in DR progression through PI3K/Akt-driven EMT, suggesting its potential as a therapeutic target.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":"75 3","pages":"100045"},"PeriodicalIF":3.2000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"LAMC1 aggravates diabetic retinopathy through PI3K/AKT signaling-regulated epithelial-mesenchymal transition in retinal pigment epithelial cells.\",\"authors\":\"Lei Liu, Yanlin Gao, Shiqi Yao\",\"doi\":\"10.1016/j.jphyss.2025.100045\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Diabetic retinopathy (DR), a leading cause of adult blindness, with LAMC1-mediated epithelial-mesenchymal transition (EMT) playing a key role. By analyzing DR-related microarray datasets (GSE60436/GSE102485) from GEO, we identified 685 differentially expressed genes (570 downregulated, 115 upregulated). Functional and WGCNA analyses linked these to PI3K/Akt signaling, revealing 11 diagnostic hub genes, including LAMC1. Western blot analysis confirmed that LAMC1 significantly upregulated in high glucose (HG)-treated ARPE-19 cells and diabetic mouse retinas. In vitro and in vivo experiments confirmed that LAMC1 promotes EMT in retinal pigment epithelial (RPE) cells via PI3K/Akt activation, enhancing migration and invasion. Conversely, LAMC1 knockdown alleviated retinal damage in diabetic mice. Our studies uncovered that LAMC1's role in DR progression through PI3K/Akt-driven EMT, suggesting its potential as a therapeutic target.</p>\",\"PeriodicalId\":16832,\"journal\":{\"name\":\"Journal of Physiological Sciences\",\"volume\":\"75 3\",\"pages\":\"100045\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2025-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Physiological Sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jphyss.2025.100045\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHYSIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Physiological Sciences","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jphyss.2025.100045","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHYSIOLOGY","Score":null,"Total":0}
LAMC1 aggravates diabetic retinopathy through PI3K/AKT signaling-regulated epithelial-mesenchymal transition in retinal pigment epithelial cells.
Diabetic retinopathy (DR), a leading cause of adult blindness, with LAMC1-mediated epithelial-mesenchymal transition (EMT) playing a key role. By analyzing DR-related microarray datasets (GSE60436/GSE102485) from GEO, we identified 685 differentially expressed genes (570 downregulated, 115 upregulated). Functional and WGCNA analyses linked these to PI3K/Akt signaling, revealing 11 diagnostic hub genes, including LAMC1. Western blot analysis confirmed that LAMC1 significantly upregulated in high glucose (HG)-treated ARPE-19 cells and diabetic mouse retinas. In vitro and in vivo experiments confirmed that LAMC1 promotes EMT in retinal pigment epithelial (RPE) cells via PI3K/Akt activation, enhancing migration and invasion. Conversely, LAMC1 knockdown alleviated retinal damage in diabetic mice. Our studies uncovered that LAMC1's role in DR progression through PI3K/Akt-driven EMT, suggesting its potential as a therapeutic target.
期刊介绍：
The Journal of Physiological Sciences publishes peer-reviewed original papers, reviews, short communications, technical notes, and letters to the editor, based on the principles and theories of modern physiology and addressed to the international scientific community. All fields of physiology are covered, encompassing molecular, cellular and systems physiology. The emphasis is on human and vertebrate physiology, but comparative papers are also considered. The process of obtaining results must be ethically sound.
Fields covered:
Adaptation and environment
Autonomic nervous function
Biophysics
Cell sensors and signaling
Central nervous system and brain sciences
Endocrinology and metabolism
Excitable membranes and neural cell physiology
Exercise physiology
Gastrointestinal and kidney physiology
Heart and circulatory physiology
Molecular and cellular physiology
Muscle physiology
Physiome/systems biology
Respiration physiology
Senses.
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