Fibrosis pp 1-23 | Cite as

Human Fibrotic Diseases: Current Challenges in Fibrosis Research

  • Joel Rosenbloom
  • Edward Macarak
  • Sonsoles Piera-Velazquez
  • Sergio A. JimenezEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1627)


Human fibrotic diseases constitute a major health problem worldwide owing to the large number of affected individuals, the incomplete knowledge of the fibrotic process pathogenesis, the marked heterogeneity in their etiology and clinical manifestations, the absence of appropriate and fully validated biomarkers, and, most importantly, the current void of effective disease-modifying therapeutic agents. The fibrotic disorders encompass a wide spectrum of clinical entities including systemic fibrotic diseases such as systemic sclerosis (SSc), sclerodermatous graft vs. host disease, and nephrogenic systemic fibrosis, as well as numerous organ-specific disorders including radiation-induced fibrosis and cardiac, pulmonary, liver, and kidney fibrosis. Although their causative mechanisms are quite diverse and in several instances have remained elusive, these diseases share the common feature of an uncontrolled and progressive accumulation of fibrotic tissue in affected organs causing their dysfunction and ultimate failure. Despite the remarkable heterogeneity in the etiologic mechanisms responsible for the development of fibrotic diseases and in their clinical manifestations, numerous studies have identified activated myofibroblasts as the common cellular element ultimately responsible for the replacement of normal tissues with nonfunctional fibrotic tissue. Critical signaling cascades, initiated primarily by transforming growth factor-β (TGF-β), but also involving numerous cytokines and signaling molecules which stimulate profibrotic reactions in myofibroblasts, offer potential therapeutic targets. Here, we briefly review the current knowledge of the molecular mechanisms involved in the development of tissue fibrosis and point out some of the most important challenges to research in the fibrotic diseases and to the development of effective therapeutic approaches for this often fatal group of disorders. Efforts to further clarify the complex pathogenetic mechanisms of the fibrotic process should be encouraged to attain the elusive goal of developing effective therapies for these serious, untreatable, and often fatal disorders.

Key words

Fibrotic disease Fibrosis Transforming growth factor-β (TGF-β) Myofibroblasts Extracellular matrix Collagen Systemic sclerosis Idiopathic pulmonary fibrosis 



Partially supported by NIH grant AR 19616 to SAJ. We thank the expert assistance of Alana Pagano and Carol Kelly in the preparation of the manuscript.


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Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  • Joel Rosenbloom
    • 1
  • Edward Macarak
    • 1
  • Sonsoles Piera-Velazquez
    • 1
  • Sergio A. Jimenez
    • 1
    Email author
  1. 1.The Joan and Joel Rosenbloom Center for Fibrotic Diseases and The Jefferson Institute of Molecular MedicineThomas Jefferson UniversityPhiladelphiaUSA

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