Developmental Signaling and Organ Fibrosis

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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