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THE ROLE OF PARATHYROID HORMONE-RELATED PROTEIN IN REGULATING NEONATAL LUNG DEVELOPMENT
by
Wei Deng
A Thesis Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(CRANIOFACIAL BIOLOGY)
August 2009
Copyright 2009 Wei Deng
Object Description
| Title | The role of parathyroid hormone-related protein in regulating neonatal lung development |
| Author | Deng, Wei |
| Author email | dengwei_07@yahoo.com; dengwei.dengwei@yahoo.com |
| Degree | Master of Science |
| Document type | Thesis |
| Degree program | Cranio-Facial Biology |
| School | School of Dentistry |
| Date defended/completed | 2009-05-27 |
| Date submitted | 2009 |
| Restricted until | Unrestricted |
| Date published | 2009-07-20 |
| Advisor (committee chair) | Paine, Michael L. |
| Advisor (committee member) |
Snead, Malcolm L. Warburton, David |
| Abstract | Parathyroid hormone-related protein (PTHrP) plays important roles in regulating a variety of developmental processes in many organs, through paracrine, autocrine and intracrine pathways. Conventional knockout of PTHrP in mice results in neonatal lethal with multiple defects including asphyxia, skeletal deformities and osteochondrodysplasia. In the present study, PTHrP conditional knockout in mouse lung epithelia versus mesenchyme has been generated. Abrogation of PTHrP specifically in lung mesenchyme results in a neonatal lethal due to lung alveolarization arrest and respiratory failure accompanied with diminished cell proliferation, loss of myofibroblasts and increased elastin accumulation. These manifestations are similar to those observed in bronchopulmonary dysplasia. No abnormality has been found in PTHrP epithelial-specific knock-out mice. Therefore, we conclude that PTHrP expression in lung mesenchyme, but not in epithelia, is essential for postnatal lung development, possibly through regulating cell proliferation, especially lung myofibroblasts, by an intracrine pathway. The fundamental knowledge obtained from this study will help understanding pathogenic mechanisms of neonatal lung disease such as bronchopulmonary dysplasia, and may also provide clues for designing novel therapeutic strategies. |
| Keyword | BPD; chronic lung disease development; neonatal lung; parathyroid hormone-related protein |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m2379 |
| Rights | Deng, Wei |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Deng-3034 |
| Archival file | uscthesesreloadpub_Volume32/etd-Deng-3034.pdf |
Description
| Title | Page 1 |
| Full text | THE ROLE OF PARATHYROID HORMONE-RELATED PROTEIN IN REGULATING NEONATAL LUNG DEVELOPMENT by Wei Deng A Thesis Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE (CRANIOFACIAL BIOLOGY) August 2009 Copyright 2009 Wei Deng |
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