Transforming growth factor beta isoforms and TGF-βR1 and TGF-βR2 expression in systemic sclerosis patients

• Published in: Clinical and experimental medicine Vol. 23; no. 2; pp. 471 - 481
• Main Authors: Lomelí-Nieto, José Alvaro, Muñoz-Valle, José Francisco, Baños-Hernández, Christian Johana, Navarro-Zarza, José Eduardo, Godínez-Rubí, Juliana Marisol, García-Arellano, Samuel, Ramírez-Dueñas, María Guadalupe, Parra-Rojas, Isela, Villanueva-Pérez, Arisbeth, Hernández-Bello, Jorge
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.06.2023; Springer Nature B.V
• Subjects: Autoantibodies; Biomarkers; Biopsy; C-reactive protein; Fibrosis; Growth factors; Hematology; Humans; Immunohistochemistry; Inflammation; Internal Medicine; Isoforms; Medicine; Medicine & Public Health; Microspheres; Oncology; Original Article; Platelets; Protein Isoforms; Scleroderma; Scleroderma, Systemic; Serum levels; Skin diseases; Skin lesions; Systemic sclerosis; Transforming Growth Factor beta - metabolism; Transforming Growth Factor beta1; Transforming growth factor-b; Transforming growth factor-b1; TGF-βR; TGF-β isoforms; Autoantibodies; sTGF-β; Systemic sclerosis
• ISSN: 1591-9528; 1591-8890; 1591-9528
• DOI: 10.1007/s10238-022-00841-0

Systemic sclerosis (SSc) is characterized by chronic inflammation and fibrosis, two processes associated with transforming growth factor β (TGF-β) functions. In the present study, we investigated the expression of TGF-β isoforms in serum and the skin distribution of TGF-β and two receptors (TGF-βR1 and TGF-βR2) and their relationship with some clinical, inflammatory, autoimmune (autoantibodies), and vascular (platelets) biomarkers in SSc patients. A total of 56 SSc patients and 120 control subjects (CS) were included. The serum levels of TGF-β isoforms were quantified by immunoassay with magnetic microspheres, and the skin biopsies were processed by immunohistochemistry. The soluble levels of the three active TGF-β isoforms were lower in SSc patients than in CS ( p  < 0.0001). However, sTGF-β1 and sTGF-β3 levels were positively correlated with C-reactive protein levels in SSc patients. Additionally, sTGF-β2 and sTGF-β3 levels were positively correlated with the number of platelets in SSc patients. In skin biopsies, TGF-β1, TGF-βR1, and TGF-βR2 expression levels were higher in SSc patients than CS. In conclusion, this is the first study showing a joint decrease of the 3 active TGF-β isoforms in SSc patients. However, TGF-β1, TGF-βR1, and TGF-βR2 are possibly increased in clinically involved skin. Therefore, it is likely that a distinct role is played by TGF-β at the local (skin lesions) and systemic levels in SSc patients.