"Wounding Response" of Fibrosis: Slow and Reversible, With Help

Rockey DC, Bell PD, and Hill JA. Fibrosis - A Common Pathway to Organ Injury and Failure. N Engl J Med 2015; 372:1138-1149. March 19, 2015. doi: 10.1056/NEJMra1300575

This review general overview of fibrosis mentions scleroderma in passing but is relevant to numerous rheumatologic conditions.

The authors propose four major phases of the fibrogenic response:

•   Initiation, driven by the primary injury
•   Activation of effector cells
•   Elaboration of extracellularmatrix
•   Deposition (and insufficient absorption) of extracellular matrix. [[{"type":"media","view_mode":"media_crop","fid":"33708","attributes":{"alt":"scleroderma","class":"media-image media-image-right","id":"media_crop_4950349815808","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"3569","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"width: 218px; height: 146px; float: right;","title":"Lung fibrosis in systemic sclerosis","typeof":"foaf:Image"}}]]

This imbalance drives the progression to fibrosis, tissue contraction, and organ deformation.  

This “wounding response” is a common pathogenic pathway in different organ systems. They share inflammatory pathways, cellular interactions, and core molecular pathways, notably the transforminggrowthfactor β (TGF-β) pathway.

This article is unusual in that it reviews the cellular and molecular themes briefly. Readers are referred to the footnotes for more detailed treatments. Suffice to say that there are important pathways that start with cell-surface receptors for TGF-β, integrins, growth factors, cytokines, and vasoactive peptides, and end with the production of extracellular matrix.

These cellular and molecular basics are the prerequisites of a clinical review of fibrosis in the heart, liver, kidney, lungs, and elsewhere.

Scar tissue is not permanent. Fibrosis, the authors remind us, is a dynamic process with actively remodeled tissue that can regress, with the elimination of effector cells and shifts in the balance of matrix synthesis and degradation. Fibrosis progresses slowly, and can be made to progress even more slowly.

The best example of reversible fibrosis is liver disease. The current state of therapy in other organs is summarized.