{"title":"Complement C5a promotes human retinal pigment epithelial cell viability and migration through SLC38A1-mediated glutamine metabolism.","authors":"Ye Sun, Yifan Hu, Shasha Luo","doi":"10.1007/s00430-025-00832-4","DOIUrl":null,"url":null,"abstract":"<p><p>The pathological basis of many visual disorders involves the abnormal viability and migration of retinal pigment epithelium (RPE) cells. Complement response disorder is a significant pathogenic factor causing some autoimmune and inflammation diseases. The complement activation product anaphylatoxin C5a signaling pathway may be associated with RPE cell dysfunction. This study aimed to analyze the molecular mechanisms by which C5a affects RPE cell viability and migration. Recombinant human complement component C5a protein stimulated RPE cells. Cell biological behavior, including cell viability, invasion, and migration were analyzed with Cell Counting Kit-8 and transwell methods. Bioinformatics analysis identified the differentially expressed genes (DEGs) involved in C5a-treated RPE cells based on RNA sequencing. SLC38A1 was knocked down or overexpressed by vector transfection to investigate its involvement in C5a-stimulated RPE cells. C5a promotes RPE cell viability and migration. C5a-induced DEGs are enriched in migration-associated pathways. C5a increased SLC38A1, and SLC38A1 knockdown or overexpression inhibited or promoted RPE cell viability and migration. Glutaminase inhibition abrogated the promoting effect of C5a and SLC38A1 on cell biological behaviors. METTL3-HNRNPC-mediated m6A modification mediated C5a-induced SLC38A1. C5a, METTL3, and SLC38A1 constituted a signaling axis in regulating cell biological behaviors of C5a-treated RPE cells. C5a promotes RPE cell viability and migration, and SLC38A1-mediated improved glutamine metabolism is the downstream signal pathway of the C5a complement pathway. The C5a complement system may target the SLC38A1 to promote RPE cell migration.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"214 1","pages":"22"},"PeriodicalIF":5.5000,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Medical Microbiology and Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00430-025-00832-4","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The pathological basis of many visual disorders involves the abnormal viability and migration of retinal pigment epithelium (RPE) cells. Complement response disorder is a significant pathogenic factor causing some autoimmune and inflammation diseases. The complement activation product anaphylatoxin C5a signaling pathway may be associated with RPE cell dysfunction. This study aimed to analyze the molecular mechanisms by which C5a affects RPE cell viability and migration. Recombinant human complement component C5a protein stimulated RPE cells. Cell biological behavior, including cell viability, invasion, and migration were analyzed with Cell Counting Kit-8 and transwell methods. Bioinformatics analysis identified the differentially expressed genes (DEGs) involved in C5a-treated RPE cells based on RNA sequencing. SLC38A1 was knocked down or overexpressed by vector transfection to investigate its involvement in C5a-stimulated RPE cells. C5a promotes RPE cell viability and migration. C5a-induced DEGs are enriched in migration-associated pathways. C5a increased SLC38A1, and SLC38A1 knockdown or overexpression inhibited or promoted RPE cell viability and migration. Glutaminase inhibition abrogated the promoting effect of C5a and SLC38A1 on cell biological behaviors. METTL3-HNRNPC-mediated m6A modification mediated C5a-induced SLC38A1. C5a, METTL3, and SLC38A1 constituted a signaling axis in regulating cell biological behaviors of C5a-treated RPE cells. C5a promotes RPE cell viability and migration, and SLC38A1-mediated improved glutamine metabolism is the downstream signal pathway of the C5a complement pathway. The C5a complement system may target the SLC38A1 to promote RPE cell migration.
期刊介绍：
Medical Microbiology and Immunology (MMIM) publishes key findings on all aspects of the interrelationship between infectious agents and the immune system of their hosts. The journal´s main focus is original research work on intrinsic, innate or adaptive immune responses to viral, bacterial, fungal and parasitic (protozoan and helminthic) infections and on the virulence of the respective infectious pathogens.
MMIM covers basic, translational as well as clinical research in infectious diseases and infectious disease immunology. Basic research using cell cultures, organoid, and animal models are welcome, provided that the models have a clinical correlate and address a relevant medical question.
The journal also considers manuscripts on the epidemiology of infectious diseases, including the emergence and epidemic spreading of pathogens and the development of resistance to anti-infective therapies, and on novel vaccines and other innovative measurements of prevention.
The following categories of manuscripts will not be considered for publication in MMIM:
submissions of preliminary work, of merely descriptive data sets without investigation of mechanisms or of limited global interest,
manuscripts on existing or novel anti-infective compounds, which focus on pharmaceutical or pharmacological aspects of the drugs,
manuscripts on existing or modified vaccines, unless they report on experimental or clinical efficacy studies or provide new immunological information on their mode of action,
manuscripts on the diagnostics of infectious diseases, unless they offer a novel concept to solve a pending diagnostic problem,
case reports or case series, unless they are embedded in a study that focuses on the anti-infectious immune response and/or on the virulence of a pathogen.
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