Parathyroid hormone-related protein-(38-64) regulates lung cell proliferation after silica injury

Am J Physiol Lung Cell Mol Physiol. 2002 Jul;283(1):L12-21. doi: 10.1152/ajplung.00308.2001.

Abstract

Inhalation of silica leads to acute lung injury and alveolar type II cell proliferation. Type II cell proliferation after hyperoxic lung injury is regulated, in part, by parathyroid hormone-related protein (PTHrP). In this study, we investigated lung PTHrP and its effects on epithelial proliferation after injury induced by silica. Lung PTHrP decreased modestly 4 days after we instilled 10 mg of silica into rat lungs and then recovered from 4 to 28 days. The number of proliferating cell nuclear antigen (PCNA)-positive type II cells was increased threefold in silica-injured lungs compared with controls. Subsequently, rats were treated with four exogenous PTHrP peptides in the silica instillate, which were administered subcutaneously daily. One peptide, PTHrP-(38-64), had consistent and significant effects on cell proliferation. PTHrP-(38-64) increased the median number of PCNA-positive cells/field nearly fourfold above controls, 380 vs. 109 (P < 0.05). Thymidine incorporation was 2.5 times higher in type II cells isolated from rats treated with PTHrP-(38-64) compared with PBS. PTHrP-(38-64) significantly increased the number of cells expressing alkaline phosphatase, a type II cell marker. This study indicates that PTHrP-(38-64) stimulates type II cell growth and may have a role in lung repair in silica-injured rats.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Count
  • Cell Division / drug effects
  • In Situ Nick-End Labeling
  • Male
  • Organ Size
  • Parathyroid Hormone / pharmacology*
  • Parathyroid Hormone-Related Protein*
  • Peptide Fragments / pharmacology*
  • Pulmonary Alveoli / drug effects
  • Pulmonary Alveoli / pathology*
  • Rats
  • Rats, Sprague-Dawley
  • Respiratory Distress Syndrome / etiology
  • Respiratory Distress Syndrome / immunology
  • Respiratory Distress Syndrome / pathology*
  • S Phase / drug effects
  • Silicon Dioxide / adverse effects*
  • Silicosis / etiology
  • Silicosis / immunology
  • Silicosis / pathology*
  • Thymidine / pharmacokinetics
  • Tritium

Substances

  • Parathyroid Hormone
  • Parathyroid Hormone-Related Protein
  • Peptide Fragments
  • parathyroid hormone-related peptide (38-64)
  • Tritium
  • Silicon Dioxide
  • Thymidine