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Understanding and Therapeutically Targeting the Scleroderma Myofibroblast

  • Scleroderma (S Bhattacharyya, Section Editor)
  • Published:
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Abstract

Purpose of Review

Myofibroblasts represent matrix-producing effector cells which both produce and maintain the pro-fibrotic microenvironment in scleroderma and other fibrotic diseases. This review first explores the origins, function, regulators, interactions, and death of myofibroblasts in fibrotic tissue and then utilizes this information to guide understanding of current and future treatments which may target these cells.

Recent Findings.

Beyond existing immunomodulatory therapy for SSc, there are an increasing number of anti-fibrotic therapies which are either under clinical study or development which may be able to effectively target myofibroblasts.

Summary

The role of myofibroblast modulation in treatment of scleroderma is a promising field with data supporting multiple new agents which may modulate myofibroblasts as anti-fibrotic therapy.

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Fig. 1

source of myofibroblasts is tissue-resident fibroblasts which are activated to become proto-myofibroblasts and eventually evolve to a more contractile phenotype as myofibroblasts. Other sources of myofibroblasts include epithelial cells via epithelial-mesenchymal transition (EMT), endothelial cells via endothelial mesenchymal transition (EndoMT), adipocytes via adipocyte mesenchymal transition (AMT), and pericytes. Myofibroblasts produce and are associated with extracellular matrix (ECM, fibrillar lattice-like structure) and ECM interacts with proteins including integrins and TGF-β to lead to intracellular Rho/ROCK signaling and activation of the TGF-β/SMAD pathway. Other relevant intracellular pathways include the Wnt, YAP/TAZ, and PDGFR/AKT pathways. IL-6 and IL-4/13 represent key profibrotic cytokines which signal through JAK/STAT pathways to activate myofibroblasts. Figure made with Biorender

Fig. 2

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  1. Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Box 695, Rochester, NY, 14642, USA

    Anthony Ocon MD & Benjamin Korman MD

  2. Department of Internal Medicine, Rochester General Hospital, Rochester, NY, USA

    Anthony Ocon MD & Sravani Lokineni MD

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Ocon, A., Lokineni, S. & Korman, B. Understanding and Therapeutically Targeting the Scleroderma Myofibroblast. Curr Treat Options in Rheum 8, 1–18 (2022). https://doi.org/10.1007/s40674-021-00189-8

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