Cellular and molecular mechanisms in fibrosis

Abstract

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More than just bricks and mortar: Fibroblasts and ECM in skin health and disease

“…Several papers in this issue explore the mechanisms of pathological skin scarring. Dees et al 11 comprehensively review the signalling and epigenetic mechanisms that drive skin fibroblast activation towards the myofibroblast state. Authors highlight the diverse roles played by TGFβ signalling and how it intersects with PDGF, FGF, STAT and WNT pathways, and which proteins within the TGFβ pathway and its downstream effectors can serve as druggable targets for anti‐fibrotic therapies.…”

“…The latter, for example, bind TGFβ and control its activation. Understanding ECM‐modulated signalling mechanisms provides novel insights into the development of fibrotic reactions (see reviews by Dees et al 11 and Macarak et al 12 in this issue) and congenital diseases such as Marfan syndrome, which is caused by fibrillin mutations (see review by Adamo et al 13 in this issue). The recent discovery of transcriptionally heterogeneous fibroblast populations means they would differentially interact with their respective ECM environment.…”

Treatment of Chronic Kidney Disease with Extracellular Vesicles from Mesenchymal Stem Cells and CD133+ Expanded Cells: A Comparative Preclinical Analysis

“…Myofibroblasts are activated by a variety of mechanisms, including paracrine signals derived from lymphocytes and macrophages. Cytokines (IL-13, IL-21, TGF-β1), chemokines (MCP-1, MIP-1β), angiogenic factors (VEGF), growth factors (GF), caspases and components of the renin-angiotensin-aldosterone system (ANG II) have been identified as important regulators of fibrosis [ 64 ]. After renal injury, pro-fibrotic factors are secreted by injured tubular epithelia and infiltrating inflammatory cells, promoting signaling events that lead to myofibroblast activation, proliferation and production of extracellular matrix [ 65 , 66 ].…”

The role of antifibrotics in the treatment of rheumatoid arthritis–associated interstitial lung disease

“… 52 Activation of TGFβ signaling, for example, by fibroblast-specific overexpression of constitutively active TGFβ receptor type 1 (TGFβRI), is sufficient to induce a systemic fibrotic disease with progressive fibrosis in multiple tissues. 52 , 54 – 56 Moreover, a number of preclinical studies have demonstrated that inhibition of TGFβ signaling exerts potent antifibrotic effects in various animal models across different organs. 57 In mice with bleomycin-induced pulmonary fibrosis, epithelial-specific deletion of TGFβRII resulted in an attenuated fibrotic response in the lung.…”