Regulation of myofibroblast activities: Calcium pulls some strings behind the scene

• Published in: Experimental cell research Vol. 316; no. 15; pp. 2390 - 2401
• Main Authors: Follonier Castella, Lysianne, Gabbiani, Giulio, McCulloch, Christopher A., Hinz, Boris
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.09.2010; Elsevier BV
• Subjects: Animals; Biochemistry; Calcium; Calcium Signaling - physiology; Calcium signalling; Cell Differentiation - physiology; Cellular biology; Collagen; Contraction; Cytoskeleton - metabolism; Cytoskeleton - physiology; Fibroblasts - metabolism; Fibroblasts - physiology; Fibrosis; Humans; Mechanotransduction; Models, Biological; Muscle Contraction - physiology; Myocytes, Smooth Muscle - cytology; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - physiology; Rho kinase; Signal transduction; Stress fiber; Wound healing; α-Smooth muscle actin; AT-II; MLCK; ROCK; Wound healing; Rho kinase; MLC; FN; MLCP; SMC; [Ca 2+] i; AJ; Stress fiber; ER; ECM; Contraction; α-Smooth muscle actin; α-SMA; ET-1; TGFβ1; PDGF; TRPC; Collagen; Fibrosis; Mechanotransduction
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2010.04.033

Myofibroblast-induced remodeling of collagenous extracellular matrix is a key component of our body's strategy to rapidly and efficiently repair damaged tissues; thus myofibroblast activity is considered crucial in assuring the mechanical integrity of vital organs and tissues after injury. Typical examples of beneficial myofibroblast activities are scarring after myocardial infarct and repair of damaged connective tissues including dermis, tendon, bone, and cartilage. However, deregulation of myofibroblast contraction causes the tissue deformities that characterize hypertrophic scars as well as organ fibrosis that ultimately leads to heart, lung, liver and kidney failure. The phenotypic features of the myofibroblast, within a spectrum going from the fibroblast to the smooth muscle cell, raise the question as to whether it regulates contraction in a fibroblast- or muscle-like fashion. In this review, we attempt to elucidate this point with a particular focus on the role of calcium signaling. We suggest that calcium plays a central role in myofibroblast biological activity not only in regulating contraction but also in mediating intracellular and extracellular mechanical signals, structurally organizing the contractile actin–myosin cytoskeleton, and establishing lines of intercellular communication.