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REVIEW: Control of Myofibroblast Differentiation and Function by Cytoskeletal Signaling

N. Sandbo1#, L. V. Smolyaninova2, S. N. Orlov2,3#*, and N. O. Dulin3,4#*

1University of Wisconsin, Department of Medicine, Madison, WI, USA

2Lomonosov Moscow State University, Faculty of Biology, Laboratory of Biomembranes, 119991 Moscow, Russia; E-mail: sergeinorlov@yandex.ru

3Siberian State Medical University, 634050 Tomsk, Russia; E-mail: ndulin@medicine.bsd.uchicago.edu

4University of Chicago, Department of Medicine, 5841 IL, USA

# These authors contributed equally to this work.

* To whom correspondence should be addressed.

Received August 7, 2016; Revision received September 14, 2016
The cytoskeleton consists of three distinct types of protein polymer structures – microfilaments, intermediate filaments, and microtubules; each serves distinct roles in controlling cell shape, division, contraction, migration, and other processes. In addition to mechanical functions, the cytoskeleton accepts signals from outside the cell and triggers additional signals to extracellular matrix, thus playing a key role in signal transduction from extracellular stimuli through dynamic recruitment of diverse intermediates of the intracellular signaling machinery. This review summarizes current knowledge about the role of cytoskeleton in the signaling mechanism of fibroblast-to-myofibroblast differentiation – a process characterized by accumulation of contractile proteins and secretion of extracellular matrix proteins, and being critical for normal wound healing in response to tissue injury as well as for aberrant tissue remodeling in fibrotic disorders. Specifically, we discuss control of serum response factor and Hippo signaling pathways by actin and microtubule dynamics as well as regulation of collagen synthesis by intermediate filaments.
KEY WORDS: myofibroblast, actin stress fibers, transcription, microtubules, differentiation, intermediate filaments, collagen synthesis

DOI: 10.1134/S0006297916130071