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Overexpression of BAG3 (Bcl2-associated athanogene 3) in serum and skin of patients with systemic sclerosis
M. De Marco1, G. Armentaro2, A. Falco3, A. Minniti4, A.L. Cammarota5, C. Iannone6, A. Basile7, A. D'ardia8, P. Zeppa9, L. Marzullo10, A. Rosati11, C. Vitali12, R. Caporali13, N. Del Papa14
- Department of Medicine, Surgery and Dentistry Schola Medica Salernitana, University of Salerno, Baronissi, and FIBROSYS s.r.l., University of Salerno, Baronissi, Italy.
- Scleroderma Clinic, UOC Clinica Reumatologica, ASST Pini-CTO, Milano, Italy.
- Department of Medicine, Surgery and Dentistry Schola Medica Salernitana, University of Salerno, Baronissi, Italy.
- Scleroderma Clinic, UOC Clinica Reumatologica, ASST Pini-CTO, Milano, Italy.
- Department of Medicine, Surgery and Dentistry Schola Medica Salernitana, University of Salerno, Baronissi, Italy.
- Scleroderma Clinic, UOC Clinica Reumatologica, ASST Pini-CTO, Milano, and Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Italy.
- Department of Medicine, Surgery and Dentistry Schola Medica Salernitana, University of Salerno, Baronissi, Italy.
- Department of Medicine, Surgery and Dentistry Schola Medica Salernitana, University of Salerno, Baronissi, and Department of Pathology, University Hospital San Giovanni di Dio e Ruggi D'Aragona, Salerno, Italy.
- Department of Medicine, Surgery and Dentistry Schola Medica Salernitana, University of Salerno, Baronissi, and Department of Pathology, University Hospital San Giovanni di Dio e Ruggi D'Aragona, Salerno, Italy.
- Department of Medicine, Surgery and Dentistry Schola Medica Salernitana, University of Salerno, Baronissi, and FIBROSYS s.r.l., University of Salerno, Baronissi, Italy.
- Department of Medicine, Surgery and Dentistry Schola Medica Salernitana, University of Salerno, Baronissi, and FIBROSYS s.r.l., University of Salerno, Baronissi, Italy.
- Rheumatology Outpatient Clinic, Mater Domini Humanitas Hospital, Castellanza, Italy.
- Scleroderma Clinic, UOC Clinica Reumatologica, ASST Pini-CTO, Milano, and Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Italy.
- Scleroderma Clinic, UOC Clinica Reumatologica, ASST Pini-CTO, Milano, and Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Italy. nicoletta.delpapa@asst-pini-cto.it
CER17646
2024 Vol.42, N°8
PI 1623, PF 1628
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PMID: 38976307 [PubMed]
Received: 05/03/2024
Accepted : 22/04/2024
In Press: 03/07/2024
Published: 14/08/2024
Abstract
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.
