The role of the TGF-SMAD signalling pathway in the etiopathogenesis of severe asthma.

Asthma is a chronic inflammatory heterogeneous disease of the lower respiratory tract characterised by the occurrence of bronchial hyper-responsiveness and paroxysmal, changeable bronchial obstruction. Transforming growth factor-beta (TGF-b) is one of the cytokines involved in mediating airway inflammation and remodelling. The level of TGF-b1 gene expression correlates with severity of symptoms. Alterations in the main SMAD signal transmission, overexpression of TGF-b genes and changes in the transcriptome cause excessive secretion of TGF-b and its increased expression in target cells, which clinically induces a moderate-severe or severe course of asthma as well as an earlier and faster disease progression. Knowledge of these processes allows clinicians to assess immune responses in patients, which affects adequate disease control and prevention of remodelling.

Transforming growth factor-ß in tumour development.

Transforming growth factor-ß (TGFß) is a ubiquitous cytokine essential for embryonic development and postnatal tissue homeostasis. TGFß signalling regulates several biological processes including cell growth, proliferation, apoptosis, immune function, and tissue repair following injury. Aberrant TGFß signalling has been implicated in tumour progression and metastasis. Tumour cells, in conjunction with their microenvironment, may augment tumourigenesis using TGFß to induce epithelial-mesenchymal transition, angiogenesis, lymphangiogenesis, immune suppression, and autophagy. Therapies that target TGFß synthesis, TGFß-TGFß receptor complexes or TGFß receptor kinase activity have proven successful in tissue culture and in animal models, yet, due to limited understanding of TGFß biology, the outcomes of clinical trials are poor. Here, we review TGFß signalling pathways, the biology of TGFß during tumourigenesis, and how protein quality control pathways contribute to the tumour-promoting outcomes of TGFß signalling.