The Role of Hedgehog Signaling in Adult Lung Regeneration and Maintenance

Abstract

As a secreted morphogen, Sonic Hedgehog (SHH) determines differential cell fates, behaviors, and functions by forming a gradient of Hedgehog (Hh) activation along an axis of Hh-receptive cells during development. Despite clearly delineated roles for Hh during organ morphogenesis, whether Hh continues to regulate cell fate and behavior in the same fashion in adult organs is less understood. Adult organs, particularly barrier organs interfacing with the ambient environment, are exposed to insults that require renewal of cellular populations to maintain structural integrity. Understanding key aspects of Hh's ability to generate an organ could translate into conceptual understanding of Hh's ability to maintain organ homeostasis and stimulate regeneration. In this review, we will summarize the current knowledge about Hh signaling in regulating adult lung regeneration and maintenance, and discuss how alteration of Hh signaling contributes to adult lung diseases.

Keywords: Hedgehog signaling; adult lung regeneration; alveolar niche; asymmetric activation; emphysema; lung fibrosis.

Figure 1

Model of asymmetric Hedgehog (Hh) activation maintaining discrete compartmental identity. We propose that differential activation of Hh is a possible mechanism in maintaining compartmental-specific identity and function in the lung. Loss of endogenous inhibitors of Hh activation could disrupt the physiological asymmetry of Hh, and lead to altered compartmental identity and structural alteration seen in lung diseases.