Hyunsik Kim, Kyu-Hye Chun, Ho-Geun Yoon, Sungryul Yu, Jung-Yoon Yoo
{"title":"在无反应的狼疮性肾炎患者中,计算机分析突出了上皮到间质转化特征的升高。","authors":"Hyunsik Kim, Kyu-Hye Chun, Ho-Geun Yoon, Sungryul Yu, Jung-Yoon Yoo","doi":"10.1177/09612033251366405","DOIUrl":null,"url":null,"abstract":"<p><p>ObjectiveLupus nephritis (LN) is a common complication in a significant proportion of systemic lupus erythematosus (SLE) patients. As a chronic autoimmune disease, LN leads to renal failure, substantially impacting patient quality of life and mortality rates. Current LN treatments primarily involve traditional immunosuppressants, such as azathioprine and mycophenolate mofetil (MMF). However, a subset of patients exhibits poor responsiveness to these therapies.MethodsTo identify genes specifically upregulated in this non-responder group, we analyzed RNA-sequencing data from the tubulointerstitial regions of LN patients and single-cell RNA-sequencing data from non-response LN patients, using datasets obtained from public databases. ResultsThis analysis revealed an increased epithelial-to-mesenchymal transition (EMT) signature in the LN patients, and identified COL3A1, TNC, and PDGFRA as commonly upregulated genes in both general LN patients and non-responder LN patients. Further validation using single-cell RNA-sequencing confirmed that these genes are predominantly expressed in renal tubular epithelial cells. Furthermore, analysis of three additional independent LN datasets confirmed that COL3A1, TNC, and PDGFRA were significantly upregulated in the tubulointerstitial regions of other LN patient cohorts. ConclusionThis study suggests that the non-responder group may exhibit enhanced EMT features, particularly involving the upregulation of COL3A1, TNC, and PDGFRA in the tubulointerstitial region. Therefore, these findings may aid in identifying potential biomarkers for difficult-to-treat patients and offer valuable insights into possible therapeutic targets for LN management.</p>","PeriodicalId":18044,"journal":{"name":"Lupus","volume":" ","pages":"1147-1157"},"PeriodicalIF":1.9000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"<i>In silico</i> analysis highlights elevation of epithelial-to-mesenchymal transition characteristics in non-responding lupus nephritis patients.\",\"authors\":\"Hyunsik Kim, Kyu-Hye Chun, Ho-Geun Yoon, Sungryul Yu, Jung-Yoon Yoo\",\"doi\":\"10.1177/09612033251366405\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>ObjectiveLupus nephritis (LN) is a common complication in a significant proportion of systemic lupus erythematosus (SLE) patients. As a chronic autoimmune disease, LN leads to renal failure, substantially impacting patient quality of life and mortality rates. Current LN treatments primarily involve traditional immunosuppressants, such as azathioprine and mycophenolate mofetil (MMF). However, a subset of patients exhibits poor responsiveness to these therapies.MethodsTo identify genes specifically upregulated in this non-responder group, we analyzed RNA-sequencing data from the tubulointerstitial regions of LN patients and single-cell RNA-sequencing data from non-response LN patients, using datasets obtained from public databases. ResultsThis analysis revealed an increased epithelial-to-mesenchymal transition (EMT) signature in the LN patients, and identified COL3A1, TNC, and PDGFRA as commonly upregulated genes in both general LN patients and non-responder LN patients. Further validation using single-cell RNA-sequencing confirmed that these genes are predominantly expressed in renal tubular epithelial cells. Furthermore, analysis of three additional independent LN datasets confirmed that COL3A1, TNC, and PDGFRA were significantly upregulated in the tubulointerstitial regions of other LN patient cohorts. ConclusionThis study suggests that the non-responder group may exhibit enhanced EMT features, particularly involving the upregulation of COL3A1, TNC, and PDGFRA in the tubulointerstitial region. Therefore, these findings may aid in identifying potential biomarkers for difficult-to-treat patients and offer valuable insights into possible therapeutic targets for LN management.</p>\",\"PeriodicalId\":18044,\"journal\":{\"name\":\"Lupus\",\"volume\":\" \",\"pages\":\"1147-1157\"},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2025-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Lupus\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/09612033251366405\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/8/1 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"RHEUMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Lupus","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/09612033251366405","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/1 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
In silico analysis highlights elevation of epithelial-to-mesenchymal transition characteristics in non-responding lupus nephritis patients.
ObjectiveLupus nephritis (LN) is a common complication in a significant proportion of systemic lupus erythematosus (SLE) patients. As a chronic autoimmune disease, LN leads to renal failure, substantially impacting patient quality of life and mortality rates. Current LN treatments primarily involve traditional immunosuppressants, such as azathioprine and mycophenolate mofetil (MMF). However, a subset of patients exhibits poor responsiveness to these therapies.MethodsTo identify genes specifically upregulated in this non-responder group, we analyzed RNA-sequencing data from the tubulointerstitial regions of LN patients and single-cell RNA-sequencing data from non-response LN patients, using datasets obtained from public databases. ResultsThis analysis revealed an increased epithelial-to-mesenchymal transition (EMT) signature in the LN patients, and identified COL3A1, TNC, and PDGFRA as commonly upregulated genes in both general LN patients and non-responder LN patients. Further validation using single-cell RNA-sequencing confirmed that these genes are predominantly expressed in renal tubular epithelial cells. Furthermore, analysis of three additional independent LN datasets confirmed that COL3A1, TNC, and PDGFRA were significantly upregulated in the tubulointerstitial regions of other LN patient cohorts. ConclusionThis study suggests that the non-responder group may exhibit enhanced EMT features, particularly involving the upregulation of COL3A1, TNC, and PDGFRA in the tubulointerstitial region. Therefore, these findings may aid in identifying potential biomarkers for difficult-to-treat patients and offer valuable insights into possible therapeutic targets for LN management.
期刊介绍:
The only fully peer reviewed international journal devoted exclusively to lupus (and related disease) research. Lupus includes the most promising new clinical and laboratory-based studies from leading specialists in all lupus-related disciplines. Invaluable reading, with extended coverage, lupus-related disciplines include: Rheumatology, Dermatology, Immunology, Obstetrics, Psychiatry and Cardiovascular Research…