Insulin increases the expression of contractile phenotypic markers in airway smooth muscle
| Autor: | Karen M. Ens, Jelte-Maarten Penninks, Hoeke A. Baarsma, S. Adriaan Nelemans, Dedmer Schaafsma, Reinoud Gosens, Gerald L. Stelmack, Bart G. J. Dekkers, Johan Zaagsma, Erin Frohwerk, Karol D. McNeill, Herman Meurs, Andrew J. Halayko, Pawan K. Sharma |
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| Přispěvatelé: | Molecular Pharmacology, Groningen Research Institute for Asthma and COPD (GRIAC) |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
hypercontractile phenotype
Time Factors phosphatidylinositol 3-kinase Transcription Genetic Pyridines Physiology medicine.medical_treatment INHALED INSULIN Receptor IGF Type 2 Receptor IGF Type 1 ASTHMATIC SUBJECTS Phosphatidylinositol 3-Kinases Contractile Proteins Smooth muscle Gene expression Rho kinase SERUM RESPONSE FACTOR Phosphorylation Rho-associated protein kinase Cells Cultured Phosphoinositide-3 Kinase Inhibitors GENE-EXPRESSION rho-Associated Kinases Microfilament Proteins Intracellular Signaling Peptides and Proteins Ribosomal Protein S6 Kinases 70-kDa Smooth Muscle Myosins Airway smooth muscle Phenotype airway smooth muscle IGF-I Trachea MYOSIN PHOSPHATASE RHO-KINASE BRONCHIAL-ASTHMA Muscle Contraction Signal Transduction medicine.medical_specialty insulin Morpholines Myocytes Smooth Muscle Protein Serine-Threonine Kinases Biology TARGETED OVEREXPRESSION Organ Culture Techniques Internal medicine Serum response factor GROWTH-FACTOR-I medicine Animals Hypoglycemic Agents RNA Messenger Cell Shape Protein Kinase Inhibitors Pancreatic hormone Insulin Calcium-Binding Proteins Muscle Smooth Cell Biology Amides Receptor Insulin Endocrinology Chromones Protein Biosynthesis Cattle |
| Zdroj: | American journal of physiology-Cell physiology, 293(1), C429-C439. AMER PHYSIOLOGICAL SOC |
| ISSN: | 0363-6143 |
| DOI: | 10.1152/ajpcell.00502.2006 |
| Popis: | We have previously demonstrated that long-term exposure of bovine tracheal smooth muscle (BTSM) strips to insulin induces a functional hypercontractile phenotype. To elucidate molecular mechanisms by which insulin might induce maturation of contractile phenotype airway smooth muscle (ASM) cells, we investigated effects of insulin stimulation in serum-free primary BTSM cell cultures on protein accumulation of specific contractile phenotypic markers and on the abundance and stability of mRNA encoding these markers. In addition, we used microscopy to assess insulin effects on ASM cell morphology, phenotype, and induction of phosphatidylinositol (PI) 3-kinase signaling. It was demonstrated that protein and mRNA levels of smooth muscle-specific contractile phenotypic markers, including sm-myosin, are significantly increased after stimulation of cultured BTSM cells with insulin (1 μM) for 8 days compared with cells treated with serum-free media, whereas mRNA stability was unaffected. In addition, insulin treatment promoted the formation of large, elongate ASM cells, characterized by dramatic accumulation of contractile phenotype marker proteins and phosphorylated p70S6K (downstream target of PI 3-kinase associated with ASM maturation). Insulin effects on protein accumulation and cell morphology were abrogated by combined pretreatment with the Rho kinase inhibitor Y-27632 (1 μM) or the PI 3-kinase inhibitor LY-294002 (10 μM), indicating that insulin increases the expression of contractile phenotypic markers in BTSM in a Rho kinase- and PI 3-kinase-dependent fashion. In conclusion, insulin increases transcription and protein expression of contractile phenotypic markers in ASM. This could have important implications for the use of recently approved aerosolized insulin formulations in diabetes mellitus. |
| Databáze: | OpenAIRE |
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