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Developmental Signaling and Organ Fibrosis

  • Activated Myofibroblasts and Fibrosis in Various Organs (T Kisseleva and Y Liu, Section Editors)
  • Published:
Current Pathobiology Reports

Abstract

Purpose of Review

Recent evidence suggests that the developmental signaling pathways—Wnt, Notch, and Hedgehog—are critically involved in organ fibrosis.

Recent Findings

Wnt, Notch, and Hedgehog signaling pathways are reactivated after organ injury and drive pathologic organ fibrosis via myofibroblast differentiation, proliferation, and extracellular matrix production. Strong evidence suggests that inhibition of these pathways might ameliorate fibrosis severity. Some conflicting results point towards highly time- and cell-specific roles of these pathways across major organs.

Summary

Usually quiescent in adult tissue homeostasis, developmental signaling pathways are reactivated after organ injury. Sustained activation of these pathways drives fibrosis and ultimately leads to an irreversible loss of organ function. Understanding the cell-specific role of Wnt, Notch, and Hedgehog signaling in fibrosis will guide the development of novel targeted therapeutics.

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Acknowledgements

This work was supported by grants of the German Research Foundation (KR-4073/3-1, SFB TRR57, P30), a grant of the European Research Council (ERC-StG 677448), a START grant of the RWTH Aachen University (101/15), and a grant of the State of Northrhinewestfalia (Return to NRW) all to RK.

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  1. Division of Nephrology and Clinical Immunology, RWTH Aachen University, Pauwelsstr 30, 52074, Aachen, Germany

    Konrad Hoeft & Rafael Kramann

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  1. Konrad Hoeft
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  2. Rafael Kramann
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Correspondence to Rafael Kramann.

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This article is part of the Topical Collection on Activated Myofibroblasts and Fibrosis in Various Organs

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Hoeft, K., Kramann, R. Developmental Signaling and Organ Fibrosis. Curr Pathobiol Rep 5, 133–143 (2017). https://doi.org/10.1007/s40139-017-0136-8

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