The Lung Elastin Matrix Undergoes Rapid Degradation Upon Adult Loss of Hox5 Function

• DOI: 10.3389/fcell.2021.767454
• Publication Date: 2021-12-01T07:38:52Z
• Authors: Mu-Hang Li; Leilani M. Marty-...; Paul R. van Ginkel; Aubrey E. McDermott; Andrew J. Rasky; Nicholas W. Lukacs; Deneen M. Wellik
• Keywords: Mesenchyme; Fibulin; Decellularization

Hox genes encode transcription factors that are critical for embryonic skeletal patterning and organogenesis. The Hoxa5 , Hoxb5 Hoxc5 paralogs expressed in the lung mesenchyme function redundantly during development. Conditional loss-of-function of these postnatal stages leads to severe defects alveologenesis, specifically generation elastin network, animals display bronchopulmonary dysplasia (BPD) or BPD-like phenotype. Here we show surprising results mesenchyme-specific loss Hox5 at adult rapid disruption mature matrix, alveolar enlargement, an emphysema-like As matrix is considered highly stable, was not predicted. Just 2 weeks after deletion, mutant significant increases space changes pulmonary function, including reduced elastance increased compliance. Examination extracellular (ECM) Tbx4rtTA; TetOCre; Hox5a f a bbcc lungs demonstrates network although underlying fibronectin, interstitial collagen basement membrane appear unaffected. An influx macrophages metalloproteinase 12 (MMP12) observed distal 3 days deletion. In culture, fibroblasts from exhibit adhesion. These findings establish novel role as regulators homeostasis.