Transcription factor Fra-2 and its emerging role in matrix deposition, proliferation and inflammation in chronic lung...

Fos-related antigen-2 (Fra-2) belongs to the activator protein 1 (AP-1) family of transcription factors and is involved in a broad variety of cellular processes, such as proliferation or differentiation. Aberrant expression of Fra-2 or regulation can lead to severe growth defects or diverse pathologies. Elevated Fra-2 expression has been described in several chronic lung diseases, such as pulmonary fibrosis, chronic obstructive pulmonary disease and asthma. However, the pathomechanisms behind the Fra-2-induced pulmonary remodelling are still not fully elucidated. Fra-2 overexpressing mice were initially described as a model of systemic sclerosis associated organ fibrosis, with predominant alterations in the lung. High levels of Fra-2 expression give rise to profound inflammation with severe remodelling of the parenchyma and the vasculature, resulting in fibrosis and pulmonary hypertension, respectively, but also alters bronchial function. In this review we discuss the central role of Fra-2 connecting inflammation, cellular proliferation and extracellular matrix deposition underlying chronic lung diseases and what we can learn for future therapeutic options.