Extracellular matrix as a driver of progressive fibrosis

Jeremy Herrera, Craig A Henke, Peter B Bitterman

Research output: Contribution to journalReview articlepeer-review

164 Scopus citations


The extracellular matrix (ECM) is dynamically tuned to optimize physiological function. Its major properties, including composition and mechanics, profoundly influence cell biology. Cell-ECM interactions operate through an integrated set of sensor and effector circuits that use several classes of receptors and signal transduction pathways. At the single-cell level, the ECM governs differentiation, metabolism, motility, orientation, proliferation, and survival. At the cell population level, the ECM provides higher-order guidance that is essential for physiological function. When pathological changes in the ECM lead to impairment of organ function, we use the term “fibrosis.” In this Review, we differentiate fibrosis initiation from progression and focus primarily on progressive lung fibrosis impairing organ function. We present a working model to explain how the altered ECM is not only a consequence but also a driver of fibrosis. Additionally, we advance the concept that fibrosis progression occurs in a fibrogenic niche that is composed of a fibrogenic ECM that nurtures fibrogenic mesenchymal progenitor cells and their fibrogenic progeny.

Original languageEnglish (US)
Pages (from-to)45-53
Number of pages9
JournalJournal of Clinical Investigation
Issue number1
StatePublished - Jan 2 2018

Bibliographical note

Funding Information:
This work was supported by NIH grants T32HL077410 (to JH), R01H125227 (to CAH), and R01HL125236 (to PBB).


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