Altered Protein Composition and Gene Expression in Strabismic Human Extraocular Muscles and Tendons
| Autor: | Amy L. Altick, Christopher S. von Bartheld, Dan Wen, L. Alan Johnson, Cheng-Yuan Feng, Andrea Agarwal, David R. Quilici |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male Proteomics collagen 0301 basic medicine Adolescent tendon extracellular matrix medicine.medical_treatment Gene Expression Muscle Proteins extraocular muscle Connective tissue Biology Extraocular muscles Mass Spectrometry Tendons Extracellular matrix Young Adult 03 medical and health sciences 0302 clinical medicine Gene expression Myosin cytokine medicine Humans Child Aged Eye Movements Strabismus Amblyopia and Neuro-Ophthalmology Reverse Transcriptase Polymerase Chain Reaction PCR array Growth factor growth factor Middle Aged Tissue inhibitor of metalloproteinase Molecular biology strabismus CTGF 030104 developmental biology medicine.anatomical_structure Oculomotor Muscles Child Preschool 030221 ophthalmology & optometry RNA Female |
| Zdroj: | Investigative Ophthalmology & Visual Science |
| ISSN: | 1552-5783 |
| Popis: | Purpose To determine whether structural protein composition and expression of key regulatory genes are altered in strabismic human extraocular muscles. Methods Samples from strabismic horizontal extraocular muscles were obtained during strabismus surgery and compared with normal muscles from organ donors. We used proteomics, standard and customized PCR arrays, and microarrays to identify changes in major structural proteins and changes in gene expression. We focused on muscle and connective tissue and its control by enzymes, growth factors, and cytokines. Results Strabismic muscles showed downregulation of myosins, tropomyosins, troponins, and titin. Expression of collagens and regulators of collagen synthesis and degradation, the collagenase matrix metalloproteinase (MMP)2 and its inhibitors, tissue inhibitor of metalloproteinase (TIMP)1 and TIMP2, was upregulated, along with tumor necrosis factor (TNF), TNF receptors, and connective tissue growth factor (CTGF), as well as proteoglycans. Growth factors controlling extracellular matrix (ECM) were also upregulated. Among 410 signaling genes examined by PCR arrays, molecules with downregulation in the strabismic phenotype included GDNF, NRG1, and PAX7; CTGF, CXCR4, NPY1R, TNF, NTRK1, and NTRK2 were upregulated. Signaling molecules known to control extraocular muscle plasticity were predominantly expressed in the tendon rather than the muscle component. The two horizontal muscles, medial and lateral rectus, displayed similar changes in protein and gene expression, and no obvious effect of age. Conclusions Quantification of proteins and gene expression showed significant differences in the composition of extraocular muscles of strabismic patients with respect to important motor proteins, elements of the ECM, and connective tissue. Therefore, our study supports the emerging view that the molecular composition of strabismic muscles is substantially altered. |
| Databáze: | OpenAIRE |
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