{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:59:38Z","timestamp":1783573178210,"version":"3.55.0"},"reference-count":48,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T00:00:00Z","timestamp":1697587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["MOST 109-2314-B040-021"],"award-info":[{"award-number":["MOST 109-2314-B040-021"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC 112-2314-B040-015"],"award-info":[{"award-number":["NSTC 112-2314-B040-015"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["CSMU-INT-111-07"],"award-info":[{"award-number":["CSMU-INT-111-07"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008641","name":"Chung Shan Medical University","doi-asserted-by":"publisher","award":["MOST 109-2314-B040-021"],"award-info":[{"award-number":["MOST 109-2314-B040-021"]}],"id":[{"id":"10.13039\/501100008641","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008641","name":"Chung Shan Medical University","doi-asserted-by":"publisher","award":["NSTC 112-2314-B040-015"],"award-info":[{"award-number":["NSTC 112-2314-B040-015"]}],"id":[{"id":"10.13039\/501100008641","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008641","name":"Chung Shan Medical University","doi-asserted-by":"publisher","award":["CSMU-INT-111-07"],"award-info":[{"award-number":["CSMU-INT-111-07"]}],"id":[{"id":"10.13039\/501100008641","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human parvovirus B19 (B19V) is a single-stranded non-enveloped DNA virus of the family Parvoviridae that has been associated with various autoimmune disorders. Systemic sclerosis (SSc) is an autoimmune connective tissue disorder with high mortality and has been linked to B19V infection. However, the precise mechanism underlying the B19V contribution to the development of SSc remains uncertain. This study investigated the impacts of the functional B19V-VP1 unique region (VP1u) in macrophages and bleomycin (BLE)-induced SSc mice. Cell experimental data showed that significantly decreased viability and migration of both B19V-VP1u-treated U937 and THP-1 macrophages are detected in the presence of celastrol. Significantly increased MMP9 activity and elevated NF-kB, MMP9, IL-6, TNF-\u03b1, and IL-1\u03b2 expressions were detected in both B19V-VP1u-treated U937 and THP-1 macrophages. Conversely, celastrol revealed an inhibitory effect on these molecules. Notably, celastrol intervened in this pathogenic process by suppressing the sPLA2 activity of B19V-VP1u and subsequently reducing the inflammatory response. Notably, the administration of B19V-VP1u exacerbated BLE-induced skin fibrosis in mice, with augmented expressions of TGF-\u03b2, IL-6, IL-17A, IL-18, and TNF-\u03b1, ultimately leading to \u03b1-SMA and collagen I deposits in the dermal regions of BLE-induced SSc mice. Altogether, this study sheds light on parvovirus B19 VP1u linked to scleroderma and aggravated dermal fibrosis.<\/jats:p>","DOI":"10.3390\/ijms242015294","type":"journal-article","created":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T09:55:06Z","timestamp":1697622906000},"page":"15294","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Effect of the Functional VP1 Unique Region of Human Parvovirus B19 in Causing Skin Fibrosis of Systemic Sclerosis"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1266-1423","authenticated-orcid":false,"given":"Der-Yuan","family":"Chen","sequence":"first","affiliation":[{"name":"Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"},{"name":"College of Medicine, China Medical University, Taichung 404, Taiwan"},{"name":"Translational Medicine Laboratory, Rheumatology and Immunology Center, China Medical University Hospital, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Chen","family":"Tzang","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, National Taiwan University, Taipei City 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan-Ming","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsu-Man","family":"Chiu","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"},{"name":"Department of Dermatology, Chung Shan Medical University Hospital, Taichung 402, Taiwan"},{"name":"School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jhen-Wei","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Hua","family":"Chuang","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Wei","family":"Kuo","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0140-9943","authenticated-orcid":false,"given":"Bor-Show","family":"Tzang","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"},{"name":"Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"},{"name":"Department of Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 402, Taiwan"},{"name":"Immunology Research Center, Chung Shan Medical University, Taichung 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsai-Ching","family":"Hsu","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"},{"name":"Department of Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 402, Taiwan"},{"name":"Immunology Research Center, Chung Shan Medical University, Taichung 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1128\/CMR.00040-16","article-title":"Human Parvoviruses","volume":"30","author":"Qiu","year":"2017","journal-title":"Clin. 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