Abstract 1903 Poster Session IV, Tuesday, 5/4 (poster 286)
Stretching of cells during pulmonary development is essential for the creation of a lung which will function at birth. Understanding how stretch affects growth and differentiation will help to elucidate the mechanisms underlying alveolar homeostasis, which is the culmination of this highly orchestrated, interactive process of cell-cell interactions. In contrast to this, developing lipid interstitial cells (LIC) fail to differentiate in vitro unless they are exposed to soluble Type II cell (TII) factors, particularly those which are stretch-regulated. Experimentally, stretching stimulates both Parathyroid Hormone-related Protein (PTHrP) and prostaglandin E2 (PGE2) secretion by TIIs. PTHrP stimulates LIC functions which are necessary for alveolar homeostasis, i.e. triglyceride (TG) uptake, Adipocyte Differentiation Related Protein (ADRP), interleukins (IL-) 6 and 11. PTHrP knock-out animals die within hours of birth due to gross immaturity of both TIIs and LICs- TIIs are devoid of lamellar bodies and apical microvillar processes; LICs, particularly those neighboring TIIs, are engorged with TG inclusions. LIC processing of ADRP-coated TG droplets appears necessary for quantitative surfactant phospholipid and protein elaboration by TIIs, coordinating these biochemically-disparate functions. Significantly, PGE2 stimulates release of ADRP-coated TG droplets by LIC but does not affect their ADRP expression; PTHrP stimulates TG uptake and ADRP expression, but not release, indicating differential regulation of these homeostatic mechanisms coordinated by cell-specific, stretch-sensitive growth factors.
Funded by NIH grant HL55268 [to JST and LPR].
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Torday, J., Londos, C., Schultz, C. et al. Distension of the Developing Lung Triggers Coordinate, Growth Factor-Mediated Cell-Cell Signal Transduction. Pediatr Res 45, 322 (1999). https://doi.org/10.1203/00006450-199904020-01919
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DOI: https://doi.org/10.1203/00006450-199904020-01919