Altered TGF beta/SMAD signaling in human and rat models of pulmonary hypertension: an old target needs attention

Sanada, T.J.; Sun, X.Q.; Happe, C.; Guignabert, C.; Tu, L.; Schalij, I.; ... ; Kurakula, K. (2021)

Article / Letter to editor

Recent translational studies highlighted the inhibition of transforming growth factor (TGF)-beta signaling as a promising target to treat pulmonary arterial hypertension (PAH). However, it remains unclear whether alterations in TGF-beta signaling are consistent between PAH patients and animal models. Therefore, we compared TGF-beta signaling in the lungs of PAH patients and rats with experimental PAH induced by monocrotaline (MCT) or SU5416+hypoxia (SuHx). In hereditary PAH (hPAH) patients, there was a moderate increase in both TGF beta R2 and pSMAD2/3 protein levels, while these were unaltered in idiopathic PAH (iPAH) patients. Protein levels of TGF beta R2 and pSMAD2/3 were locally increased in the pulmonary vasculature of PAH rats under both experimental conditions. Conversely, the protein levels of TGF beta R2 and pSMAD2/3 were reduced in SuHx while slightly increased in MCT. mRNA levels of plasminogen activator inhibitor (PAI)-1 were increased only in MCT animals and such an increase was not observed in SuHx rats or in iPAH and hPAH patients. In conclusion, our data demonstrate considerable discrepancies in TGF beta-SMAD signaling between iPAH and hPAH patients, as well as between patients and rats with experimental PAH.

• pulmonary arterial hypertension
• TGF-βsignaling
• SMADs
• animal models of pulmonary hypertension

• All authors: Sanada, T.J.; Sun, X.Q.; Happe, C.; Guignabert, C.; Tu, L.; Schalij, I.; Bogaard, H.J.; Goumans, M.J.; Kurakula, K.
• Date: 2021-01-01
• Journal: Cells
• Volume: 10
• Issue: 1
• DOI: doi:10.3390/cells10010084
• Link: https://europepmc.org/articles/pmc7825543?pdf=render