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

Clin Exp Med. 2023 Jun;23(2):471-481. doi: 10.1007/s10238-022-00841-0. Epub 2022 May 29.

Abstract

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.

Keywords: Autoantibodies; Systemic sclerosis; TGF-β isoforms; TGF-βR; sTGF-β.

MeSH terms

  • Biomarkers
  • Humans
  • Protein Isoforms
  • Scleroderma, Systemic*
  • Transforming Growth Factor beta* / metabolism
  • Transforming Growth Factor beta1

Substances

  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Biomarkers
  • Protein Isoforms