Pulmonary sarcoidosis is a granulomatous inflammatory disease of unknown aetiology that causes a fibrotic process and sarcoidosis-associated fibrosis in the advanced stage. The key feature is the dysregulated activity of the TGFB signalling pathway. Although the TGF-beta signalling pathway has been the subject of many investigations in sarcoidosis, more information about the parallel expression of three TGF-beta ligands, their receptors and secondary messengers is needed.
      We aimed to assess the relative expression of the following genes: TGF-beta1-3, TGF-betaR1 and 2, SMURF and SMAD2, 4, 5 and 7 in mRNA extracted from unseparated bronchoalveolar lavage cells obtained from patients with pulmonary sarcoidosis (n=35) and controls (n=25) using the Real-time PCR method.
      Among TGF-beta ligands, the relative expression of TGF-beta1 (p=0.02) was elevated in our patients with pulmonary sarcoidosis compared to controls. The expressions of TGF-beta2 and TGF-beta3 did not differ between our patients and controls. Both receptors, TGF-betaR1 (p=0.0001) and TGF-betaR2 (p=0.0001), were up-regulated in our patients. The secondary messengers SMAD2, 4, 5 and 7 were elevated (for all p=0.0001), and SMURF (p>0.05) had a similar expression in our patients compared to controls. Our results suggest that the TGF-beta receptors and their secondary messengers contribute to fibrotic changes in pulmonary sarcoidosis more than the TGF-beta ligand. A stimulation by other ligands or/and the genetic factors of these receptors could explain their elevated expression and the elevated secondary messengers in our patients.

Grant support: IGA UP: LF_2023_007, 2024_005