Margot De Marco, Giuseppe Armentaro, Antonia Falco, Antonina Minniti, Anna Lisa Cammarota, Claudia Iannone, Anna Basile, Angela D'Ardia, Pio Zeppa, Liberato Marzullo, Alessandra Rosati, Claudio Vitali, Roberto Caporali, Nicoletta Del Papa
{"title":"系统性硬化症患者血清和皮肤中 BAG3(Bcl2-相关基因 3)的过度表达。","authors":"Margot De Marco, Giuseppe Armentaro, Antonia Falco, Antonina Minniti, Anna Lisa Cammarota, Claudia Iannone, Anna Basile, Angela D'Ardia, Pio Zeppa, Liberato Marzullo, Alessandra Rosati, Claudio Vitali, Roberto Caporali, Nicoletta Del Papa","doi":"10.55563/clinexprheumatol/ua07a2","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>BAG3 (Bcl2-associated athanogene3) is able to induce the transformation of cancer-associated fibroblasts to alpha smooth muscle actin (a-SMA) positive (+) myofibroblasts. In systemic sclerosis (SSc), a-SMA+ myofibroblasts also play an important role in the progression of fibrosis in the skin and involved internal organs. The aim of the study was to investigate whether BAG3 is overexpressed in SSc and may be a biomarker of fibrogenesis.</p><p><strong>Methods: </strong>BAG3 serum levels were measured in 106 patients with SSc, 47 with the limited (lc) and 59 the diffuse (dc) SSc, and in age- and sex-matched healthy controls (HC). BAG3 levels were then compared according to their clinical subset, nailfold video-capillaroscopic (NVC) patterns, interstitial lung disease (ILD, and correlated with modified Rodnan skin score (mRSS) and global disease activity. BAG3 expression was also investigated in skin biopsies of 8 dcSSc patients.</p><p><strong>Results: </strong>BAG3 serum levels were significantly higher in dcSSc (143.3 pg/mL, 95%CI 78-208.5) than in HC (0.68 pg/mL, 95%CI 0.13-1.23), and were significantly higher in patients with late NVC pattern and ILD but did not correlate with disease activity and mRSS. Of note, BAG3 was strongly expressed in the skin biopsies of dcSSc patients.</p><p><strong>Conclusions: </strong>BAG3 is overexpressed in dcSSc patients and may contribute to skin and organ fibrosis by prompting the transition of fibroblasts into myofibroblasts and increasing their survival. Thus, BAG3 may play an important role in SSc fibrotic pathogenesis and be a potential biomarker of fibrosis. Further research on its role as a therapeutic target is warranted.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Overexpression of BAG3 (Bcl2-associated athanogene 3) in serum and skin of patients with systemic sclerosis.\",\"authors\":\"Margot De Marco, Giuseppe Armentaro, Antonia Falco, Antonina Minniti, Anna Lisa Cammarota, Claudia Iannone, Anna Basile, Angela D'Ardia, Pio Zeppa, Liberato Marzullo, Alessandra Rosati, Claudio Vitali, Roberto Caporali, Nicoletta Del Papa\",\"doi\":\"10.55563/clinexprheumatol/ua07a2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>BAG3 (Bcl2-associated athanogene3) is able to induce the transformation of cancer-associated fibroblasts to alpha smooth muscle actin (a-SMA) positive (+) myofibroblasts. In systemic sclerosis (SSc), a-SMA+ myofibroblasts also play an important role in the progression of fibrosis in the skin and involved internal organs. The aim of the study was to investigate whether BAG3 is overexpressed in SSc and may be a biomarker of fibrogenesis.</p><p><strong>Methods: </strong>BAG3 serum levels were measured in 106 patients with SSc, 47 with the limited (lc) and 59 the diffuse (dc) SSc, and in age- and sex-matched healthy controls (HC). BAG3 levels were then compared according to their clinical subset, nailfold video-capillaroscopic (NVC) patterns, interstitial lung disease (ILD, and correlated with modified Rodnan skin score (mRSS) and global disease activity. BAG3 expression was also investigated in skin biopsies of 8 dcSSc patients.</p><p><strong>Results: </strong>BAG3 serum levels were significantly higher in dcSSc (143.3 pg/mL, 95%CI 78-208.5) than in HC (0.68 pg/mL, 95%CI 0.13-1.23), and were significantly higher in patients with late NVC pattern and ILD but did not correlate with disease activity and mRSS. Of note, BAG3 was strongly expressed in the skin biopsies of dcSSc patients.</p><p><strong>Conclusions: </strong>BAG3 is overexpressed in dcSSc patients and may contribute to skin and organ fibrosis by prompting the transition of fibroblasts into myofibroblasts and increasing their survival. Thus, BAG3 may play an important role in SSc fibrotic pathogenesis and be a potential biomarker of fibrosis. Further research on its role as a therapeutic target is warranted.</p>\",\"PeriodicalId\":10274,\"journal\":{\"name\":\"Clinical and experimental rheumatology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical and experimental rheumatology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.55563/clinexprheumatol/ua07a2\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/3 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"RHEUMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and experimental rheumatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.55563/clinexprheumatol/ua07a2","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/3 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
Overexpression of BAG3 (Bcl2-associated athanogene 3) in serum and skin of patients with systemic sclerosis.
Objectives: BAG3 (Bcl2-associated athanogene3) is able to induce the transformation of cancer-associated fibroblasts to alpha smooth muscle actin (a-SMA) positive (+) myofibroblasts. In systemic sclerosis (SSc), a-SMA+ myofibroblasts also play an important role in the progression of fibrosis in the skin and involved internal organs. The aim of the study was to investigate whether BAG3 is overexpressed in SSc and may be a biomarker of fibrogenesis.
Methods: BAG3 serum levels were measured in 106 patients with SSc, 47 with the limited (lc) and 59 the diffuse (dc) SSc, and in age- and sex-matched healthy controls (HC). BAG3 levels were then compared according to their clinical subset, nailfold video-capillaroscopic (NVC) patterns, interstitial lung disease (ILD, and correlated with modified Rodnan skin score (mRSS) and global disease activity. BAG3 expression was also investigated in skin biopsies of 8 dcSSc patients.
Results: BAG3 serum levels were significantly higher in dcSSc (143.3 pg/mL, 95%CI 78-208.5) than in HC (0.68 pg/mL, 95%CI 0.13-1.23), and were significantly higher in patients with late NVC pattern and ILD but did not correlate with disease activity and mRSS. Of note, BAG3 was strongly expressed in the skin biopsies of dcSSc patients.
Conclusions: BAG3 is overexpressed in dcSSc patients and may contribute to skin and organ fibrosis by prompting the transition of fibroblasts into myofibroblasts and increasing their survival. Thus, BAG3 may play an important role in SSc fibrotic pathogenesis and be a potential biomarker of fibrosis. Further research on its role as a therapeutic target is warranted.
期刊介绍:
Clinical and Experimental Rheumatology is a bi-monthly international peer-reviewed journal which has been covering all clinical, experimental and translational aspects of musculoskeletal, arthritic and connective tissue diseases since 1983.