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

2002 ◽  
Vol 283 (1) ◽  
pp. L130-L135 ◽  
Author(s):  
J. S. Torday ◽  
V. K. Rehan
Keyword(s):  
Pulmonary Surfactant ◽  
Feedback Loop ◽  
Related Protein ◽  
Phospholipid Synthesis ◽  
Alveolar Epithelial ◽  
Parathyroid Hormone Related Protein ◽  
Surfactant Production ◽  
Adipose Differentiation ◽  
Paracrine Actions ◽  
Stimulation Of

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.

scholarly journals Role of adipose differentiation-related protein in lung surfactant production: a reassessment

2006 ◽  
Vol 47 (11) ◽  
pp. 2367-2373 ◽  
Author(s):  
Amy L. Magra ◽  
Pamela S. Mertz ◽  
John S. Torday ◽  
Constantine Londos
Keyword(s):  
Lung Surfactant ◽  
Related Protein ◽  
Surfactant Production ◽  
Adipose Differentiation

scholarly journals Organization of the Indian hedgehog – parathyroid hormone-related protein system in the postnatal growth plate

2011 ◽  
Vol 47 (1) ◽  
pp. 99-107 ◽  
Author(s):  
Michael Chau ◽  
Patricia Forcinito ◽  
Anenisia C Andrade ◽  
Anita Hegde ◽  
Sohyun Ahn ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Growth Plate ◽  
Feedback Loop ◽  
Postnatal Growth ◽  
Indian Hedgehog ◽  
Related Protein ◽  
Functional Changes ◽  
Growth Cartilage ◽  
Embryonic Growth ◽  
Parathyroid Hormone Related Protein

In embryonic growth cartilage, Indian hedgehog (Ihh) and parathyroid hormone-related protein (PTHrP) participate in a negative feedback loop that regulates chondrocyte differentiation. Postnatally, this region undergoes major structural and functional changes. To explore the organization of the Ihh–PTHrP system in postnatal growth plate, we microdissected growth plates of 7-day-old rats into their constituent zones and assessed expression of genes participating in the Ihh–PTHrP feedback loop.Ihh, Patched 1, Smoothened,Gli1, Gli2, Gli3, andPthr1were expressed in regions analogous to the expression domains in embryonic growth cartilage. However, PTHrP was expressed in resting zone cartilage, a site that differs from the embryonic source, the periarticular cells. We then used mice in whichlacZhas replaced coding sequences ofGli1and thus serves as a marker for active hedgehog signaling. At 1, 4, 8, and 12 weeks of age,lacZexpression was detected in a pattern analogous to that of embryonic cartilage. The findings support the hypothesis that the embryonic Ihh–PTHrP feedback loop is maintained in the postnatal growth plate except that the source of PTHrP has shifted to a more proximal location in the resting zone.

Parathyroid hormone-related protein reduces alveolar epithelial cell proliferation during lung injury in rats

2000 ◽  
Vol 279 (1) ◽  
pp. L194-L200 ◽  
Author(s):  
Randolph H. Hastings ◽  
John T. Berg ◽  
Daphne Summers-Torres ◽  
Douglas W. Burton ◽  
Leonard J. Deftos
Keyword(s):  
Cell Proliferation ◽  
Parathyroid Hormone ◽  
Lung Injury ◽  
Alveolar Epithelial Cell ◽  
Epithelial Cell Proliferation ◽  
Related Protein ◽  
High Power Field ◽  
Alveolar Epithelial ◽  
Parathyroid Hormone Related Protein ◽  
Pthrp Expression

Parathyroid hormone-related protein (PTHrP) is a growth inhibitor for alveolar type II cells and could be a regulatory factor for alveolar epithelial cell proliferation after lung injury. We investigated lung PTHrP expression in rats exposed to 85% oxygen. Lung levels of PTHrP were significantly decreased between 4 and 8 days of hyperoxia, concurrent with increased expression of proliferating cell nuclear antigen and increased incorporation of 5-bromo-2′-deoxyuridine (BrdU) into DNA in lung corner cells. PTHrP receptor was present in both normal and hyperoxic lung. To test whether the fall in PTHrP was related to cell proliferation, we instilled PTHrP into lungs on the fourth day of hyperoxia. Eight hours later, BrdU labeling in alveolar corner cells was 3.2 ± 0.4 cells/high-power field in hyperoxic PBS-instilled rats compared with 0.5 ± 0.3 cells/high-power field in PTHrP-instilled rats ( P < 0.01). Thus PTHrP expression changes in response to lung injury due to 85% oxygen and may regulate cell proliferation.

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