Stretch-stimulated surfactant synthesis is coordinated by the paracrine actions of PTHrP and leptin

Am J Physiol Lung Cell Mol Physiol. 2002 Jul;283(1):L130-5. doi: 10.1152/ajplung.00380.2001.

Abstract

Intrauterine lung development, culminating in physiological pulmonary surfactant production by epithelial type II (TII) cells, is driven by fluid distension through unknown mechanisms. Differentiation of alveolar epithelial and mesenchymal cells is mediated by soluble factors like parathyroid hormone-related protein (PTHrP), a stretch-sensitive TII cell product. PTHrP stimulates pulmonary surfactant production by a paracrine feedback loop mediated by leptin, a soluble product of the mature lipofibroblast (LF). When LFs and TIIs are stretched in coculture, there is a fivefold increase in surfactant phospholipid synthesis that can be "neutralized" by inhibitors of PTHrP or leptin, implicating a paracrine feedback loop in this mechanism. Stretching LFs stimulates PTHrP binding (2.5-fold) and downstream stimulation of triglyceride uptake quantitatively (15-25%) due to upregulation of adipose differentiation-related protein expression. Stretching TII cells increases leptin stimulation of their surfactant phospholipid synthesis threefold, suggesting that retrograde signaling by leptin to TII cells is also stretch sensitive. We conclude that the effect of stretch on alveolar LF and TII differentiation is coordinated by PTHrP, leptin, and their receptors.

MeSH terms

  • Animals
  • Cells, Cultured
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Gene Expression / physiology
  • Leptin / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Paracrine Communication / physiology*
  • Parathyroid Hormone-Related Protein
  • Perilipin-2
  • Phosphatidylcholines / biosynthesis
  • Pregnancy
  • Proteins / metabolism*
  • Pulmonary Surfactants / biosynthesis*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Parathyroid Hormone, Type 1
  • Receptors, Parathyroid Hormone / metabolism
  • Stress, Mechanical
  • Triglycerides / pharmacokinetics
  • Up-Regulation / physiology

Substances

  • Leptin
  • Membrane Proteins
  • Parathyroid Hormone-Related Protein
  • Perilipin-2
  • Phosphatidylcholines
  • Plin2 protein, rat
  • Proteins
  • Pulmonary Surfactants
  • Receptor, Parathyroid Hormone, Type 1
  • Receptors, Parathyroid Hormone
  • Triglycerides