Journal
JOURNAL OF PATHOLOGY
Volume 229, Issue 2, Pages 298-309Publisher
WILEY
DOI: 10.1002/path.4104
Keywords
ECM; myofibroblast; fibrosis
Funding
- Canadian Institutes of Health Research [210820]
- Collaborative Health Research Programme (CIHR/NSERC) [1004005]
- Canada Foundation for Innovation
- Ontario Research Fund [26653]
- Heart and Stroke Foundation Ontario [NA7086]
- European Union [237946]
- National Institutes of Health [R01 HL085083, R01 HL109118, U01 HL111016]
- Drews Sarcoidosis Research Fund
- Martin Edward Galvin Fund for Pulmonary Fibrosis Research at the University of Michigan
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL085083, R01HL109118, T32HL007749, U01HL111016] Funding Source: NIH RePORTER
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Myofibroblasts, and the extracellular matrix (ECM) in which they reside, are critical components of wound healing and fibrosis. The ECM, traditionally viewed as the structural elements within which cells reside, is actually a functional tissue whose components possess not only scaffolding characteristics, but also growth factor, mitogenic, and other bioactive properties. Although it has been suggested that tissue fibrosis simply reflects an exuberant wound-healing response, examination of the ECM and the roles of myofibroblasts during fibrogenesis instead suggest that the organism may be attempting to recapitulate developmental programmes designed to regenerate functional tissue. Evidence of this is provided by the temporospatial re-emergence of embryonic ECM proteins by fibroblasts and myofibroblasts that induce cellular programmatic responses intended to produce a functional tissue. In the setting of wound healing (or physiological fibrosis), this occurs in a highly regulated and exquisitely choreographed fashion which results in cessation of haemorrhage, restoration of barrier integrity, and re-establishment of tissue function. However, pathological tissue fibrosis, which oftentimes causes organ dysfunction and significant morbidity or mortality, likely results from dysregulation of normal wound-healing processes or abnormalities of the process itself. This review will focus on the myofibroblast ECM and its role in both physiological and pathological fibrosis, and will discuss the potential for therapeutically targeting ECM proteins for treatment of fibrotic disorders.
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