{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T05:28:11Z","timestamp":1741066091761,"version":"3.38.0"},"reference-count":57,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T00:00:00Z","timestamp":1740960000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"name":"Basic and Applied Basic Research Project of Guangdong Province of China","award":["2024A1515013218"],"award-info":[{"award-number":["2024A1515013218"]}]},{"name":"Research team project of Prevention and Treatment of Diabetic Cardiomyopathy with Integrated Chinese and Western medicine","award":["2024ZZ06"],"award-info":[{"award-number":["2024ZZ06"]}]},{"name":"Medical Science and Technology Research Fund of Guangdong Province","award":["A2021311"],"award-info":[{"award-number":["A2021311"]}]},{"name":"Open Project of NHC Key Laboratory of Assisted Circulation and Vascular Diseases","award":["KF202101"],"award-info":[{"award-number":["KF202101"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n               <jats:title>Background<\/jats:title>\n               <jats:p>Cardiac fibroblasts (CFs) play a vital role in the physiological and pathological processes of the heart. Previous studies have demonstrated that high glucose stimulation induces the transformation of CFs into myofibroblasts, contributing to cardiac fibrogenesis. However, <jats:italic>in vivo<\/jats:italic> experiments have predominantly utilized adult animals, whereas most <jats:italic>in vitro<\/jats:italic> studies have focused on CFs derived from neonatal animals. The responses of CFs from different age groups to high glucose levels remain unclear. This study aimed to investigate transcriptional alterations in CFs at distinct developmental stages in response to high glucose exposure.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Methods<\/jats:title>\n               <jats:p>CFs were isolated from neonatal (S1, 0\u20133 days), juvenile (S2, 3\u20134 weeks), adult (S3, 10\u201313 weeks), and aged (S4, 20 months) rats. CFs were exposed to normal (5.5 mM, NG) or high glucose (33 mM, HG). The cellular RNA was extracted for sequencing and analysis. Differentially expressed genes (DEGs) were validated by quantitative real-time PCR.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Results<\/jats:title>\n               <jats:p>After NG treatment, fibrosis and inflammation-related gene expression in CFs (<jats:italic>e.g.<\/jats:italic>, <jats:italic>Col8a1<\/jats:italic>, <jats:italic>Col8a2<\/jats:italic>, <jats:italic>IL-6<\/jats:italic>, <jats:italic>Ccl2<\/jats:italic>, <jats:italic>Ccl20<\/jats:italic>, <jats:italic>Mmp2<\/jats:italic> and <jats:italic>Mmp9<\/jats:italic>) increased with age, while proliferation-related genes (MCM family, <jats:italic>Sox10<\/jats:italic>, <jats:italic>Sox11<\/jats:italic>) decreased. HG treatment most affected S3-CFs, showing 228 DEGs; it suppressed growth-related genes (<jats:italic>Adra1d<\/jats:italic>, <jats:italic>Htr2b<\/jats:italic>) and enhanced inflammatory genes (<jats:italic>IL-6<\/jats:italic>, <jats:italic>Olr1<\/jats:italic>). In S1-CFs, 197 inflammation-rich genes were upregulated under HG. S4-CFs displayed 166 DEGs, mostly metabolic downregulation (<jats:italic>G6pc<\/jats:italic>). S2-CFs had the fewest DEGs (112), focusing on cell metabolism.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Conclusions<\/jats:title>\n               <jats:p>Fibrosis- and inflammation-associated gene expression in CFs showed an age-dependent stepwise elevation. CFs from distinct developmental stages responded differently to HG stimulation, with S3-CFs exhibiting the most pronounced response. These findings highlight the developmental characteristics of CFs and provide implications for the selection of appropriate CFs to investigate diabetes-associated cardiac fibrosis.<\/jats:p>\n            <\/jats:sec>","DOI":"10.7717\/peerj.19040","type":"journal-article","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T08:15:38Z","timestamp":1740989738000},"page":"e19040","source":"Crossref","is-referenced-by-count":0,"title":["Effect of high glucose on the gene expression profiling in cardiac fibroblasts from rats at different ages"],"prefix":"10.7717","volume":"13","author":[{"given":"Quqian","family":"Mo","sequence":"first","affiliation":[{"name":"Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angyu","family":"Zhan","sequence":"additional","affiliation":[{"name":"Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruining","family":"Bai","sequence":"additional","affiliation":[{"name":"Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaoling","family":"Lin","sequence":"additional","affiliation":[{"name":"Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaojiao","family":"Feng","sequence":"additional","affiliation":[{"name":"Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tongjun","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zijian","family":"Lao","sequence":"additional","affiliation":[{"name":"Department of Emergency, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China"},{"name":"NHC Key Laboratory of Assisted Circulation and Vascular Diseases, Sun Yat-sen University, Guangzhou,  Guangdong Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Guangzhou First People\u2019s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keke","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Emergency, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China"},{"name":"NHC Key Laboratory of Assisted Circulation and Vascular Diseases, Sun Yat-sen University, Guangzhou,  Guangdong Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianglu","family":"Rong","sequence":"additional","affiliation":[{"name":"Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lexun","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4443","published-online":{"date-parts":[[2025,3,3]]},"reference":[{"key":"10.7717\/peerj.19040\/ref-1","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1161\/circresaha.116.309202","article-title":"A simplified, langendorff-free method for concomitant isolation of viable cardiac myocytes and nonmyocytes from the adult mouse heart","volume":"119","author":"Ackers-Johnson","year":"2016","journal-title":"Circulation Research"},{"key":"10.7717\/peerj.19040\/ref-2","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.ahj.2018.05.016","article-title":"Patterns of glucose-lowering medication use in patients with type 2 diabetes and heart failure. 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