Descriptive transcriptome analysis of tendon derived fibroblasts following in-vitro exposure to advanced glycation end products.

Autor: Patel SH; Department of Health and Kinesiology, Purdue University, West Lafayette, IN, United States of America., Mendias CL; Hospital for Special Surgery, New York, NY, United States of America.; Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY, United States of America., Carroll CC; Department of Health and Kinesiology, Purdue University, West Lafayette, IN, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2022 Jul 26; Vol. 17 (7), pp. e0271770. Date of Electronic Publication: 2022 Jul 26 (Print Publication: 2022).
DOI: 10.1371/journal.pone.0271770
Abstrakt: Background: Tendon pathologies affect a large portion of people with diabetes. This high rate of tendon pain, injury, and disease appears to manifest independent of well-controlled HbA1c and fasting blood glucose. Advanced glycation end products (AGEs) are elevated in the serum of those with diabetes. In vitro, AGEs severely impact tendon fibroblast proliferation and mitochondrial function. However, the extent that AGEs impact the tendon cell transcriptome has not been evaluated.
Objective: The purpose of this study was to investigate transcriptome-wide changes that occur to tendon-derived fibroblasts following treatment with AGEs. We propose to complete a descriptive approach to pathway profiling to broaden our mechanistic understanding of cell signaling events that may contribute to the development of tendon pathology.
Methods: Rat Achilles tendon fibroblasts were treated with glycolaldehyde-derived AGEs (200μg/ml) for 48 hours in normal glucose (5.5mM) conditions. In addition, total RNA was isolated, and the PolyA+ library was sequenced.
Results: We demonstrate that tendon fibroblasts treated with 200μg/ml of AGEs differentially express 2,159 gene targets compared to fibroblasts treated with an equal amount of BSA-Control. Additionally, we report in a descriptive and ranked fashion 21 implicated cell-signaling pathways.
Conclusion: Our findings suggest that AGEs disrupt the tendon fibroblast transcriptome on a large scale and that these pathways may contribute to the development and progression of diabetic tendinopathy. Specifically, pathways related to cell cycle progression and extracellular matrix remodeling were affected in our data set and may play a contributing role in the development of diabetic tendon complications.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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