| First Author | RuizdelRio J | Year | 2022 |
| Journal | J Immunol | Volume | 209 |
| Issue | 1 | Pages | 38-48 |
| PubMed ID | 35715007 | Mgi Jnum | J:329562 |
| Mgi Id | MGI:7345958 | Doi | 10.4049/jimmunol.2100430 |
| Citation | RuizdelRio J, et al. (2022) Profibrotic Role of Inducible Heat Shock Protein 90alpha Isoform in Systemic Sclerosis. J Immunol 209(1):38-48 |
| abstractText | Systemic sclerosis (SSc) is an autoimmune disease that affects skin and multiple internal organs. TGF-beta, a central trigger of cutaneous fibrosis, activates fibroblasts with the involvement of the stress-inducible chaperone heat shock protein 90 isoform alpha (Hsp90alpha). Available evidence supports overexpression and secretion of Hsp90alpha as a feature in profibrotic pathological conditions. The aim of this work is to investigate the expression and function of Hsp90alpha in experimental models of skin fibrosis such as human fibroblasts, C57BL/6 mice, and in human SSc. For this purpose, we generated a new experimental model based on doxorubicin administration with improved characteristics with respect to the bleomycin model. We visualized disease progression in vivo by fluorescence imaging. In this work, we obtained Hsp90alpha mRNA overexpression in human skin fibroblasts, in bleomycin- and doxorubicin-induced mouse fibrotic skin, and in lungs of bleomycin- and doxorubicin-treated mice. Hsp90alpha-deficient mice showed significantly decreased skin thickness compared with wild-type mice in both animal models. In SSc patients, serum Hsp90alpha levels were increased in patients with lung involvement and in patients with the diffuse form of SSc (dSSc) compared with patients with the limited form of SSc. The serum Hsp90alpha levels of patients dSSc were correlated with the Rodnan score and the forced vital capacity variable. These results provide new supportive evidence of the contribution of the Hsp90alpha isoform in the development of skin fibrosis. In SSc, these results indicated that higher serum levels were associated with dSSc and lung fibrosis. |
