Myofibroblasts

Abstract

Myofibroblasts are activated in response to tissue injury with the primary task to repair lost or damaged extracellular matrix. Enhanced collagen secretion and subsequent contraction - scarring - are part of the normal wound healing response and crucial to restore tissue integrity. Due to myofibroblasts ability to repair but not regenerate, accumulation of scar tissue is always associated with reduced organ performance. This is a fair price to pay by the body for not falling apart. Whereas myofibroblasts typically vanish after successful repair, dysregulation of the normal repair process can lead to persistent myofibroblast activation, for instance by chronic inflammation or mechanical stress in the tissue. Excessive repair leads to the accumulation of stiff collagenous ECM contractures - fibrosis - with dramatic consequences for organ function. The clinical need to terminate detrimental myofibroblast activities has stimulated researchers to answer a number of essential questions: where do myofibroblasts come from, what are the factors leading to their activation, how do we discriminate myofibroblasts from other cells, what is the molecular basis for their contractile activity, and how can we stop or at least control them? This article reviews the current state of the myofibroblast literature by emphasizing their role in ocular repair and fibrosis. It appears that although the eye is quite an extraordinary organ, ocular myofibroblasts behave or misbehave just like their siblings in other organs.

Neuronal Protein 3.1 Deficiency Leads to Reduced Cutaneous Scar Collagen Deposition and Tensile Strength due to Impaired Transforming Growth Factor-β1 to -β3 Translation

“…These showed that P311 stimulated smooth muscle actin production, increased proliferation, promoted migration, and increased contractility of both MFs and HFs, all consistent with induction of the activated state 49 and the transition to myofibroblasts. 50 In addition, P311 had an antiapoptotic effect in both cell types. All these P311-induced changes are consistent with a profibrogenic phenotype and help to understand how P311 contributes to the scar formation.…”

Contribution of collagen adhesion receptors to tissue fibrosis

“…Detailed reviews on the origin and activation of myofibroblasts are beyond the scope of this review and are given elsewhere (Falke et al 2015;Hinz 2016;Hinz et al 2012;Micallef et al 2012;Postlethwaite et al 2004;van Putten et al 2015). In some tissues, smooth muscle cells, pericytes, and cells derived from epithelial-mesenchymal transformation can also contribute to increased collagen synthesis and collagen deposition in the interstitium Kisseleva and Brenner 2008).…”

The Role of Myeloid Lineage Cells on Skin Healing and Skin Regeneration

“…Recently, lineage tracing studies in mice have demonstrated that hair-follicle stem cells transiently contribute to wound re-epithelialization by producing cells that migrate to the epithelial layer and differentiate [15]. Beneath the epidermal layer, wound contraction is mediated by the transformation of fibroblasts into contractile myofibroblasts by mechanical signals and TGF-β [16]. Dermal compartment repair is not just mediated by fibroblasts.…”