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.
Clin Exp Rheumatol. 2024 Aug;42(8):1623-1628. doi: 10.55563/clinexprheumatol/ua07a2. Epub 2024 Jul 3.
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.
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.
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.
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.
BAG3（Bcl2 相关抗凋亡基因 3）能够诱导癌症相关成纤维细胞向α平滑肌肌动蛋白（α-SMA）阳性（+）肌成纤维细胞转化。在系统性硬化症（SSc）中，α-SMA+肌成纤维细胞在皮肤和内脏纤维化的进展中也起着重要作用。本研究旨在探讨 BAG3 是否在 SSc 中过度表达，是否可能成为纤维化的生物标志物。
检测了 106 例 SSc 患者（47 例局限型（lc）和 59 例弥漫型（dc））、47 例年龄和性别匹配的健康对照者（HC）的 BAG3 血清水平。然后根据其临床亚型、甲襞视频毛细血管镜（NVC）模式、间质性肺病（ILD）将 BAG3 水平进行比较，并与改良 Rodnan 皮肤评分（mRSS）和整体疾病活动相关。还在 8 例 dcSSc 患者的皮肤活检标本中研究了 BAG3 的表达。
dcSSc 患者的 BAG3 血清水平（143.3 pg/mL，95%CI 78-208.5）明显高于 HC（0.68 pg/mL，95%CI 0.13-1.23），且在晚期 NVC 模式和ILD 患者中更高，但与疾病活动度和 mRSS 无相关性。值得注意的是，BAG3 在 dcSSc 患者的皮肤活检标本中强烈表达。
BAG3 在 dcSSc 患者中过度表达，通过促使成纤维细胞向肌成纤维细胞转化并增加其存活，可能导致皮肤和器官纤维化。因此，BAG3 可能在 SSc 纤维化发病机制中起重要作用，并可能成为纤维化的潜在生物标志物。进一步研究其作为治疗靶点的作用是必要的。
