Abstract | PURPOSE OF REVIEW: Organ fibrosis is a lethal component of scleroderma. The hallmark of scleroderma fibrosis is extensive extracellular matrix (ECM) deposition by activated myofibroblasts, specialized hyper-contractile cells that promote ECM remodeling and matrix stiffening. The purpose of this review is to discuss novel mechanistic insight into myofibroblast activation in scleroderma. RECENT FINDINGS: Matrix stiffness, traditionally viewed as an end point of organ fibrosis, is now recognized as a critical regulator of tissue fibrogenesis that hijacks the normal physiologic wound-healing program to promote organ fibrosis. Here, we discuss how matrix stiffness orchestrates fibrosis by controlling three fundamental pro-fibrotic mechanisms: (a) mechanoactivation of myofibroblasts, (b) integrin-mediated latent transforming growth factor beta 1 (TGF-β1) activation, and (c) activation of non-canonical TGF-β1 signaling pathways. We also summarize novel therapeutic targets for anti-fibrotic therapy based on the mechanobiology of scleroderma. Future research on mechanobiology of scleroderma may lead to important clinical applications such as improved diagnosis and treatment of patients with scleroderma and other fibrotic-related diseases.
|
Authors | Alba Santos, David Lagares |
Journal | Current rheumatology reports
(Curr Rheumatol Rep)
Vol. 20
Issue 1
Pg. 2
(01 19 2018)
ISSN: 1534-6307 [Electronic] United States |
PMID | 29349703
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
|
Chemical References |
- Anti-Inflammatory Agents
- Transforming Growth Factor beta1
|
Topics |
- Anti-Inflammatory Agents
(pharmacology, therapeutic use)
- Extracellular Matrix
(drug effects, metabolism, pathology)
- Fibrosis
- Humans
- Myofibroblasts
(drug effects, metabolism, pathology)
- Scleroderma, Systemic
(drug therapy, metabolism, pathology, physiopathology)
- Signal Transduction
(drug effects, genetics, physiology)
- Transforming Growth Factor beta1
(metabolism, physiology)
- Wound Healing
(drug effects, physiology)
|