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Insulin-like growth factor-I stimulates differentiation of ATII cells to ATI-like cells through activation of Wnt5a.
- Source :
-
American journal of physiology. Lung cellular and molecular physiology [Am J Physiol Lung Cell Mol Physiol] 2013 Aug 01; Vol. 305 (3), pp. L222-8. Date of Electronic Publication: 2013 May 24. - Publication Year :
- 2013
-
Abstract
- Alveolar type II (ATII) epithelial cells play a crucial role in the repair and remodeling of the lung following injury. ATII cells have the capability to proliferate and differentiate into alveolar type I (ATI) cells in vivo and into an ATI-like phenotype in vitro. While previous reports indicate that the differentiation of ATII cells into ATI cells is a complex biological process, the underlying mechanism responsible for differentiation is not fully understood. To investigate factors involved in this differentiation in culture, we used a PCR array and identified several genes that were either up- or downregulated in ATI-like cells (day 6 in culture) compared with day 2 ATII cells. Insulin-like growth factor-I (IGF-I) mRNA was increased nearly eightfold. We found that IGF-I was increased in the culture media of ATI-like cells and demonstrated a significant role in the differentiation process. Treatment of ATII cells with recombinant IGF-I accelerated the differentiation process, and this effect was abrogated by the IGF-I receptor blocker PQ401. We found that Wnt5a, a member of the Wnt-Frizzled pathway, was activated during IGF-I-mediated differentiation. Both protein kinase C and β-catenin were transiently activated during transdifferentiation. Knocking down Wnt5a using small-interfering RNA abrogated the differentiation process as indicated by changes in the expression of an ATII cell marker (prosurfactant protein-C). Treatment of wounded cells with either IGF-I or Wnt5a stimulated wound closure. These results suggest that IGF-I promotes differentiation of ATII to ATI cells through the activation of a noncanonical Wnt pathway.
- Subjects :
- Aminoquinolines pharmacology
Animals
Cell Differentiation
Cell Proliferation
Cell Transdifferentiation
Cells, Cultured
Enzyme Activation
Insulin-Like Growth Factor I genetics
Insulin-Like Growth Factor I pharmacology
Mice
Phenylurea Compounds pharmacology
Protein Kinase C metabolism
RNA Interference
RNA, Messenger metabolism
RNA, Small Interfering
Rats
Recombinant Proteins pharmacology
Wnt Proteins genetics
Wnt Proteins pharmacology
Wnt-5a Protein
Wound Healing
beta Catenin metabolism
Insulin-Like Growth Factor I physiology
Pulmonary Alveoli cytology
Pulmonary Alveoli metabolism
Wnt Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1504
- Volume :
- 305
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Lung cellular and molecular physiology
- Publication Type :
- Academic Journal
- Accession number :
- 23709620
- Full Text :
- https://doi.org/10.1152/ajplung.00014.2013