Pulmonary administration of integrin-nanoparticles regenerates collapsed alveoli
| Autor: | Hitomi Sakai, Chikamasa Yamashita, Hiroshi Kubo, Michiko Horiguchi, Hisako Kojima |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Pathology medicine.medical_specialty Integrin Retinoic acid Pharmaceutical Science Tretinoin Biology Integrin alpha1beta1 Pulmonary Disease Chronic Obstructive chemistry.chemical_compound Glucosides In vivo Administration Inhalation medicine Animals Humans Regeneration Protein kinase B Cells Cultured Mice Inbred ICR Lung Pancreatic Elastase Microarray analysis techniques Stem Cells Cell Differentiation respiratory system Integrin alphaVbeta3 Pulmonary Alveoli medicine.anatomical_structure chemistry Cancer research biology.protein Nanoparticles Phosphorylation Stem cell |
| Zdroj: | Journal of Controlled Release. 187:167-174 |
| ISSN: | 0168-3659 |
| Popis: | Chronic obstructive pulmonary disease (COPD) is an intractable pulmonary disease, causes widespread and irreversible alveoli collapse. In search of a treatment target molecule, which is able to regenerate collapsed alveoli, we sought to identify a factor that induces differentiation in human alveolar epithelial stem cells using all-trans retinoic acid (ATRA), whose alveolar repair capacity has been reported in animal experiments. When human alveolar epithelial stem cells were exposed to ATRA at a concentration of 10μM for over seven days, approximately 20% of the cells differentiated into each of the type-I and type-II alveolar epithelial cells that constitute the alveoli. In a microarray analysis, integrin-α1 and integrin-β3 showed the largest variation in the ATRA-treated group compared with the controls. Furthermore, the effect of the induction of differentiation in human alveolar epithelial stem cells using ATRA was suppressed by approximately one-fourth by siRNA treatments with integrin α1 and integrin β3. These results suggested that integrin α1 and β3 are factors responsible for the induction of differentiation in human alveolar epithelial stem cells. We accordingly investigated whether integrin nanoparticles also had a regenerative effect in vivo. Elastase-induced COPD model mouse was produced, and the alveolar repair effect of pulmonary administration using nanoparticles of integrin protein was evaluated by X-ray CT scanning. Improvement in the CT value in comparison with an untreated group indicated that there was an alveolar repair effect. In this study, it was shown that the differentiation-inducing effect on human alveolar epithelial stem cells by ATRA was induced by increased expression of integrin, and that the induced integrin enhanced phosphorylation signaling of AKT, resulting in inducing differentiations. Furthermore, the study demonstrated that lung administration of nanoparticles with increased solubility and stability of integrin repaired the alveolus of an Elastase-induced COPD model mouse. Those results show that those integrin nanoparticles are effective as novel COPD treatment target compounds. |
| Databáze: | OpenAIRE |
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