FHL-1 interacts with human RPE cells through the α5β1 integrin and confers protection against oxidative stress
| العنوان: | FHL-1 interacts with human RPE cells through the α5β1 integrin and confers protection against oxidative stress |
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| المؤلفون: | Martin J. Humphries, Paul N. Bishop, Nadhim Bayatti, Maja Søberg Udsen, Rawshan Choudhury, Viranga Tilakaratna, Selina McHarg, Richard Scharff, Ewa Szula, Simon J. Clark, Janet A. Askari |
| المصدر: | Scientific Reports Choudhury, R, Bayatti, N, Scharff, R, Szula, E, Tilakaratna, V, Udsen, M, Mcharg, S, Askari, J, Humphries, M J, Bishop, P & Clark, S 2021, ' FHL-1 interacts with human RPE cells through the α5β1 integrin and confers protection against oxidative stress ', Scientific Reports, vol. 11, no. 1, 14175 . https://doi.org/10.1038/s41598-021-93708-5 Choudhury, R, Bayatti, N, Scharff, R, Szula, E, Tilakaratna, V, Udsen, M S, McHarg, S, Askari, J A, Humphries, M J, Bishop, P N & Clark, S J 2021, ' FHL-1 interacts with human RPE cells through the α5β1 integrin and confers protection against oxidative stress ', Scientific Reports, vol. 11, 14175 . https://doi.org/10.1038/s41598-021-93708-5 Scientific Reports, Vol 11, Iss 1, Pp 1-17 (2021) |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Integrins, Cell, Muscle Proteins, Cell Communication, Retinal Pigment Epithelium, 0302 clinical medicine, Laminin, Telomerase, Muscle Proteins/metabolism, Cells, Cultured, RGD motif, LIM Domain Proteins/metabolism, Multidisciplinary, biology, Cell Death, Chemistry, Intracellular Signaling Peptides and Proteins, Extracellular matrix, LIM Domain Proteins, Cell biology, Complement cascade, Intracellular Signaling Peptides and Proteins/metabolism, medicine.anatomical_structure, Medicine, Immobilized Proteins/metabolism, Integrin alpha5beta1, Protein Binding, Science, Cell fate determination, Article, Telomerase/metabolism, 03 medical and health sciences, medicine, Humans, Retinal Pigment Epithelium/metabolism, Retina, Extracellular Matrix/metabolism, eye diseases, HSPA1A, Oxidative Stress, 030104 developmental biology, Immobilized Proteins, Gene Expression Regulation, Cell culture, Integrin alpha5beta1/metabolism, Unfolded protein response, biology.protein, sense organs, Gene expression, 030217 neurology & neurosurgery |
| الوصف: | Retinal pigment epithelial (RPE) cells that underlie the neurosensory retina are essential for the maintenance of photoreceptor cells and hence vision. Interactions between the RPE and their basement membrane, i.e. the inner layer of Bruch’s membrane, are essential for RPE cell health and function, but the signals induced by Bruch’s membrane engagement, and their contributions to RPE cell fate determination remain poorly defined. Here, we studied the functional role of the soluble complement regulator and component of Bruch’s membrane, Factor H-like protein 1 (FHL-1). Human primary RPE cells adhered to FHL-1 in a manner that was eliminated by either mutagenesis of the integrin-binding RGD motif in FHL-1 or by using competing antibodies directed against the α5 and β1 integrin subunits. These short-term experiments reveal an immediate protein-integrin interaction that were obtained from primary RPE cells and replicated using the hTERT-RPE1 cell line. Separate, longer term experiments utilising RNAseq analysis of hTERT-RPE1 cells bound to FHL-1, showed an increased expression of the heat-shock protein genes HSPA6, CRYAB, HSPA1A and HSPA1B when compared to cells bound to fibronectin (FN) or laminin (LA). Pathway analysis implicated changes in EIF2 signalling, the unfolded protein response, and mineralocorticoid receptor signalling as putative pathways. Subsequent cell survival assays using H2O2 to induce oxidative stress-induced cell death suggest hTERT-RPE1 cells had significantly greater protection when bound to FHL-1 or LA compared to plastic or FN. These data show a non-canonical role of FHL-1 in protecting RPE cells against oxidative stress and identifies a novel interaction that has implications for ocular diseases such as age-related macular degeneration. |
| وصف الملف: | application/pdf |
| تدمد: | 2045-2322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ecd44c6c515f5cf3e410767874f2acb8 https://pubmed.ncbi.nlm.nih.gov/34239032 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....ecd44c6c515f5cf3e410767874f2acb8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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