Tissue Development, Repair, and Remodeling - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 735

Optimal airway healing and repair is controlled by both bronchial epithelial and
endothelial cells of the perfusing bronchial vasculature [ 1477 ]. 74 Both cell types
work synergistically and produce multiple mediators, although at different lev-
els [ 1477 ]: 75 (1) prostaglandins such as PGe2, a potent bronchodilator that stabilizes
extracellular matrix in airway walls and augments vascular permeability; (2) growth
factors such as TGF 2 as well as FGF2 that stimulates the proliferation

of vascular endothelial and bronchial smooth muscle cells; (3) cytokines such
as CSF2; (4) chemokines such as CCL2 and CXCL8; and (5) soluble adhesion
molecules VCAM1 S and ICAM1 S . An ordered cellular architecture is dispensable
to achieve these effects.
Notch signaling is involved in the specification of the ciliated lineage in airways.
Transcription factor FoxJ1 expressed in ciliated cells of adult lungs, is required in
late stages of ciliogenesis. Factor FoxJ1 can then serve as a marker of precursor
cells already committed to the ciliated lineage. FoxJ1

β 1andTGF β

ciliated cells transiently
change their morphology in response to lung injury, but neither proliferate nor
transdifferentiate during repair [ 1393 ].
Nevertheless, ciliated cells can function as progenitors in response to different
types of damages and according to proximal or distal injury location, i.e., trachea
and primary bronchi or distal bronchi, bronchioles, and bronchoalveolar duct
junctions. Ciliated cells may transdifferentiate into mucus-secreting cells in murine
models of asthma and viral infection [ 1393 ].

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11.8 Vascular Tissue Remodeling

The wall of the heart and the blood vessels bear stresses applied by the flowing
blood. The wall reacts, and then strengthens in high-stress regions. The short-
term wall adaptation can indeed lead to long-term remodeling when abnormal
stress magnitude and oscillation amplitude during the cardiac cycle are sensed.
An integrative model incorporates behaviors at various length and time scales
in order to efficiently describe structure-function relationships of physiological
systems.

74 Airway epithelial and vascular endothelial cells cultured separately or together secrete different
patterns of repair mediators. Furthermore, their release levels depend on whether these cells are
embedded into a matrix or not [ 1477 ]. Matrix-embedded endothelial cells express lower amounts
of MHC class-2 molecules, chemokines, and adhesion molecules than endothelial cells cultured
as a sheet. Matrix-embedded endothelial cell synthesizes smaller quantities of chemokines CCL2
and CXCL8 and soluble adhesion molecules sICAM1 and sVCAM1 in cocultures with bronchial
epithelial cells than alone.
75 Matrix-embedded bronchial epithelial cells secrete higher amounts of PGe2, gmCSF, and TGF β 1
than vascular endothelial cells [ 1477 ]. Conversely, matrix-embedded bronchial epithelial cells
produce lower levels of FGF2 than vascular endothelial cells.