title: Parathyroid hormone-related protein-(38-64) regulates lung cell proliferation after silica injury.
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.
authors.affiliation: Research, Anesthesiology, and Medicine Services, Veterans Affairs San Diego Healthcare System, San Diego, California 92161, USA. rhhastings@ucsd.edu
authors.forename: Randolph H
authors.initials: RH
authors.lastname: Hastings
authors.forename: Angela
authors.initials: A
authors.lastname: Asirvatham
authors.forename: Rick
authors.initials: R
authors.lastname: Quintana
authors.forename: Rebeca
authors.initials: R
authors.lastname: Sandoval
authors.forename: Ruchika
authors.initials: R
authors.lastname: Dutta
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Burton
authors.forename: Leonard J
authors.initials: LJ
authors.lastname: Deftos
mesh_terms: D000818:Animals; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D008297:Male; D009929:Organ Size; D010281:Parathyroid Hormone / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D016196:S Phase / Q000187:drug effects; D012822:Silicon Dioxide / Q000009:adverse effects*; D012829:Silicosis / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D013936:Thymidine / Q000493:pharmacokinetics; D014316:Tritium
chemical_list: D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; C459881:parathyroid hormone-related peptide (38-64); D014316:Tritium; D012822:Silicon Dioxide; D013936:Thymidine