Epithelial repair mechanisms in the lung

Lynn M. Crosby, Christopher Waters

Research output: Contribution to journalReview article

378 Citations (Scopus)

Abstract

The recovery of an intact epithelium following lung injury is critical for restoration of lung homeostasis. The initial processes following injury include an acute inflammatory response, recruitment of immune cells, and epithelial cell spreading and migration upon an autologously secreted provisional matrix. Injury causes the release of factors that contribute to repair mechanisms including members of the epidermal growth factor and fibroblast growth factor families (TGF-α, KGF, HGF), chemokines (MCP-1), interleukins (IL-1β, IL-2, IL-4, IL-13), and prostaglandins (PGE2), for example. These factors coordinate processes involving integrins, matrix materials (fibronectin, collagen, laminin), matrix metalloproteinases (MMP-1, MMP-7, MMP-9), focal adhesions, and cytoskeletal structures to promote cell spreading and migration. Several key signaling pathways are important in regulating these processes, including sonic hedgehog, Rho GTPases, MAP kinase pathways, STAT3, and Wnt. Changes in mechanical forces may also affect these pathways. Both localized and distal progenitor stem cells are recruited into the injured area, and proliferation and phenotypic differentiation of these cells leads to recovery of epithelial function. Persistent injury may contribute to the pathology of diseases such as asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis. For example, dysregulated repair processes involving TGF-β and epithelial-mesenchymal transition may lead to fibrosis. This review focuses on the processes of epithelial restitution, the localization and role of epithelial progenitor stem cells, the initiating factors involved in repair, and the signaling pathways involved in these processes.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume298
Issue number6
DOIs
StatePublished - Jun 1 2010

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Matrix Metalloproteinases
Stem Cells
Interleukin-1
Lung
Cell Movement
Wounds and Injuries
Epithelial Cells
rho GTP-Binding Proteins
Matrix Metalloproteinase 1
Stem Cell Factor
Focal Adhesions
Epithelial-Mesenchymal Transition
Interleukin-13
Fibroblast Growth Factors
Pulmonary Fibrosis
Recovery of Function
Lung Injury
Laminin
Fibronectins
Chemokines

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

Epithelial repair mechanisms in the lung. / Crosby, Lynn M.; Waters, Christopher.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 298, No. 6, 01.06.2010.

Research output: Contribution to journalReview article

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