Respiratory Distress and Early Neonatal Lethality in Hspa4l/Hspa4 Double-Mutant Mice
| Autor: | Belal A. Mohamed, Torsten Held, Amal Z. Barakat, Manar Elkenani, Christian Mühlfeld, Ibrahim M. Adham, Jörg Männer |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Lung Diseases
Pulmonary and Respiratory Medicine Programmed cell death Pathology medicine.medical_specialty Mice 129 Strain Genotype Clinical Biochemistry Apoptosis Gestational Age Biology Andrology HSPA4 Mice Pulmonary hypoplasia Heat shock protein Morphogenesis medicine Animals Abnormalities Multiple HSP70 Heat-Shock Proteins HSP110 Heat-Shock Proteins Lung Molecular Biology Cell Proliferation Mice Knockout Respiratory Distress Syndrome Newborn Cell growth Respiration Ubiquitination Gene Expression Regulation Developmental Epithelial Cells Cell Biology medicine.disease Ubiquitinated Proteins Epithelium Mice Inbred C57BL Phenotype medicine.anatomical_structure |
| Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 50:817-824 |
| ISSN: | 1535-4989 1044-1549 |
| Popis: | Heat shock proteins HSPA4L and HSPA4 are closely related members of the HSP110 family and act as cochaperones. We generated Hspa4l(-/-)Hspa4(-/-) mice to investigate a functional complementarity between HSPA4L and HSPA4 during embryonic development. Hspa4l(-/-)Hspa4(-/-) embryos exhibited marked pulmonary hypoplasia and neonatal death. Compared with lungs of wild-type, Hspa4l(-/-), and Hspa4(-/-) embryos, Hspa4l(-/-)Hspa4(-/-) lungs were characterized by diminished saccular spaces and increased mesenchymal septa. Mesenchymal hypercellularity was determined to be due to an increased cell proliferation index and decreased cell death. A significant increase in expression levels of prosurvival protein B cell leukemia/lymphoma 2 may be the cause for inhibition of apoptotic process in lungs of Hspa4(-/-)Hspa4l(-/-) embryos. Accumulation of glycogen and diminished expression of surfactant protein B, prosurfactant protein C, and aquaporin 5 in saccular epithelium suggested impaired maturation of type II and type I pneumocytes in the Hspa4l(-/-)Hspa4(-/-) lungs. Further experiments showed a significant accumulation of ubiquitinated proteins in the lungs of Hspa4l(-/-)Hspa4(-/-) embryos, indicating an impaired chaperone activity. Our study demonstrates that HSPA4L and HSPA4 collaborate in embryonic lung maturation, which is necessary for adaptation to air breathing at birth. |
| Databáze: | OpenAIRE |
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