TY - JOUR
T1 - Mechano-therapeutics
T2 - Targeting Mechanical Signaling in Fibrosis and Tumor Stroma
AU - Tschumperlin, Daniel J.
AU - Lagares, David
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/8
Y1 - 2020/8
N2 - Pathological remodeling of the extracellular matrix (ECM) by activated myofibroblasts is a hallmark of fibrotic diseases and desmoplastic tumors. Activation of myofibroblasts occurs in response to fibrogenic tissue injury as well as in tumor-associated fibrotic reactions. The molecular determinants of myofibroblast activation in fibrosis and tumor stroma have traditionally been viewed to include biochemical agents, such as dysregulated growth factor and cytokine signaling, which profoundly alter the biology of fibroblasts, ultimately leading to overexuberant matrix deposition and fibrosis. More recently, compelling evidence has shown that altered mechanical properties of the ECM such as matrix stiffness are major drivers of tissue fibrogenesis by promoting mechano-activation of fibroblasts. In this Review, we discuss new insights into the role of the biophysical microenvironment in the amplified activation of fibrogenic myofibroblasts during the development and progression of fibrotic diseases and desmoplastic tumors. We also summarize novel therapeutic targets for anti-fibrotic therapy based on the mechanobiology of tissue fibrosis and tumor stroma, a class of drugs known as “mechano-therapeutics”.
AB - Pathological remodeling of the extracellular matrix (ECM) by activated myofibroblasts is a hallmark of fibrotic diseases and desmoplastic tumors. Activation of myofibroblasts occurs in response to fibrogenic tissue injury as well as in tumor-associated fibrotic reactions. The molecular determinants of myofibroblast activation in fibrosis and tumor stroma have traditionally been viewed to include biochemical agents, such as dysregulated growth factor and cytokine signaling, which profoundly alter the biology of fibroblasts, ultimately leading to overexuberant matrix deposition and fibrosis. More recently, compelling evidence has shown that altered mechanical properties of the ECM such as matrix stiffness are major drivers of tissue fibrogenesis by promoting mechano-activation of fibroblasts. In this Review, we discuss new insights into the role of the biophysical microenvironment in the amplified activation of fibrogenic myofibroblasts during the development and progression of fibrotic diseases and desmoplastic tumors. We also summarize novel therapeutic targets for anti-fibrotic therapy based on the mechanobiology of tissue fibrosis and tumor stroma, a class of drugs known as “mechano-therapeutics”.
KW - CAFs
KW - Fibrosis
KW - Mechano-therapeutics
KW - Mechanobiology
KW - Myofibroblasts
KW - Tumor Stroma
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UR - http://www.scopus.com/inward/citedby.url?scp=85084485700&partnerID=8YFLogxK
U2 - 10.1016/j.pharmthera.2020.107575
DO - 10.1016/j.pharmthera.2020.107575
M3 - Review article
C2 - 32437826
AN - SCOPUS:85084485700
SN - 0163-7258
VL - 212
JO - Pharmacology and Therapeutics
JF - Pharmacology and Therapeutics
M1 - 107575
ER -