STAT3 in tissue fibrosis: is there a role in the lung?
Fibrosis is defined as an excessive deposition of connective tissue components that results in the destruction of normal tissue architecture and compromises organ function. When fibrosis occurs in the major organs such as the lung, for example in idiopathic pulmonary fibrosis, it inevitably leads to organ failure and premature death of the afflicted individual. Current evidence suggests that fibrosis initially develops along the same pathway as normal wound healing, although there is chronic progression of the disease without resolution, suggesting the control of intracellular processes that occur during wound healing is disturbed. It follows then that determining where this control is lost is key to preventing and treating this condition. The IL-6 cytokine family is a group of pleiotropic cytokines produced by a variety of cells in response to inflammatory stimuli. These cytokines are grouped together on the basis of overlapping functions, and common usage of gp130 as part of their multimeric receptor complexes. Activation of these receptor complexes results in the recruitment and phosphorylation of the latent transcription factor STAT-3 which induces a gene program involved in cell differentiation and proliferation. STAT3 also induces expression of a number of inhibitors including SOCS-3. In this manuscript we review the available literature on the IL-6/gp-130 family of cytokines and their role in regulating fibrosis. Despite a large number of studies in mouse models as well as human cells in vitro, the role of these cytokines or STAT3 activated by other cytokines in the development of fibrosis remains unclear.
UBC James Hogg Research Centre, Heart + Lung Institute, University of British Columbia, V6Z 1Y6 Canada. dknight@mrl.ubc.ca
Darryl
D
Knight
Steven E
SE
Mutsaers
Cecilia M
CM
Prêle
D000818:Animals; D050822:Cytokine Receptor gp130 / Q000378:metabolism*; D018450:Disease Progression; D005355:Fibrosis; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000150:complications / Q000473:pathology*; D015850:Interleukin-6 / Q000378:metabolism*; D051379:Mice; D009102:Multiple Organ Failure / Q000209:etiology; D050796:STAT3 Transcription Factor / Q000378:metabolism*
D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D050822:Cytokine Receptor gp130