Details

Autor(en) / Beteiligte

• Peng, Tien
• Frank, David B.
• Kadzik, Rachel S.
• Morley, Michael P.
• Rathi, Komal S.
• Wang, Tao
• Zhou, Su
• Cheng, Lan
• Lu, Min Min
• Morrisey, Edward E.

Titel

Hedgehog actively maintains adult lung quiescence and regulates repair and regeneration

Ist Teil von

• Nature (London), 2015-10, Vol.526 (7574), p.578-582

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2015

Quelle

Psychology & Behavioral Sciences Collection

Beschreibungen/Notizen

• It is generally thought that the quiescence of tissue is not actively maintained, but rather a state reflecting the absence of proliferative signal; here the authors find that quiescence is actively maintained by paracrine hedgehog signalling provided by the epithelium in the mouse adult lung, and that hedgehog is dynamically regulated during injury repair and resolution for proper restoration of tissue homeostasis after injury. Active maintenance of tissue quiescence This study questions the common assumption that the quiescence of tissue is not maintained actively, but is a state reflecting the absence of proliferative signal. Edward Morrisey and colleagues report that quiescence in mesenchymal tissue in the mouse adult lung is actively maintained by paracrine sonic hedgehog signalling provided by the adjacent epithelium. They show that this signal needs to be downregulated after injury to allow proliferation of the lung mesenchyme, which is key for tissue repair. Postnatal tissue quiescence is thought to be a default state in the absence of a proliferative stimulus such as injury. Although previous studies have demonstrated that certain embryonic developmental programs are reactivated aberrantly in adult organs to drive repair and regeneration 1 , 2 , 3 , it is not well understood how quiescence is maintained in organs such as the lung, which displays a remarkably low level of cellular turnover 4 , 5 . Here we demonstrate that quiescence in the adult lung is an actively maintained state and is regulated by hedgehog signalling. Epithelial-specific deletion of sonic hedgehog ( Shh ) during postnatal homeostasis in the murine lung results in a proliferative expansion of the adjacent lung mesenchyme. Hedgehog signalling is initially downregulated during the acute phase of epithelial injury as the mesenchyme proliferates in response, but returns to baseline during injury resolution as quiescence is restored. Activation of hedgehog during acute epithelial injury attenuates the proliferative expansion of the lung mesenchyme, whereas inactivation of hedgehog signalling prevents the restoration of quiescence during injury resolution. Finally, we show that hedgehog also regulates epithelial quiescence and regeneration in response to injury via a mesenchymal feedback mechanism. These results demonstrate that epithelial–mesenchymal interactions coordinated by hedgehog actively maintain postnatal tissue homeostasis, and deregulation of hedgehog during injury leads to aberrant repair and regeneration in the lung.