{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T18:28:16Z","timestamp":1770748096915,"version":"3.49.0"},"reference-count":54,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T00:00:00Z","timestamp":1626220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1083131, 1084083, 1143601"],"award-info":[{"award-number":["1083131, 1084083, 1143601"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Coagulopathies common to patients with diabetes and chronic kidney disease (CKD) are not fully understood. Fibrin deposits in the kidney suggest the local presence of clotting factors including tissue factor (TF). In this study, we investigated the effect of glucose availability on the synthesis of TF by cultured human kidney tubular epithelial cells (HTECs) in response to activation of protease-activated receptor 2 (PAR2). PAR2 activation by peptide 2f-LIGRLO-NH2 (2F, 2 \u00b5M) enhanced the synthesis and secretion of active TF (~45 kDa) which was blocked by a PAR2 antagonist (I-191). Treatment with 2F also significantly increased the consumption of glucose from the cell medium and lactate secretion. Culturing HTECs in 25 mM glucose enhanced TF synthesis and secretion over 5 mM glucose, while addition of 5 mM 2-deoxyglucose (2DOG) significantly decreased TF synthesis and reduced its molecular weight (~40 kDa). Blocking glycosylation with tunicamycin also reduced 2F-induced TF synthesis while reducing its molecular weight (~36 kDa). In conclusion, PAR2-induced TF synthesis in HTECs is enhanced by culture in high concentrations of glucose and suppressed by inhibiting either PAR2 activation (I-191), glycolysis (2DOG) or glycosylation (tunicamycin). These results may help explain how elevated concentrations of glucose promote clotting abnormities in diabetic kidney disease. The application of PAR2 antagonists to treat CKD should be investigated further.<\/jats:p>","DOI":"10.3390\/ijms22147532","type":"journal-article","created":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T10:13:42Z","timestamp":1626257622000},"page":"7532","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["PAR2-Induced Tissue Factor Synthesis by Primary Cultures of Human Kidney Tubular Epithelial Cells Is Modified by Glucose Availability"],"prefix":"10.3390","volume":"22","author":[{"given":"Tyrone L. R.","family":"Humphries","sequence":"first","affiliation":[{"name":"Centre for Kidney Disease Research, Translational Research Institute, Faulty of Medicine, The University of Queensland at the Princess Alexandra, Brisbane, QLD 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunyu","family":"Shen","sequence":"additional","affiliation":[{"name":"Centre for Kidney Disease Research, Translational Research Institute, Faulty of Medicine, The University of Queensland at the Princess Alexandra, Brisbane, QLD 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abishek","family":"Iyer","sequence":"additional","affiliation":[{"name":"Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia"},{"name":"Centre for Inflammation and Disease Research, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5491-3460","authenticated-orcid":false,"given":"David W.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Centre for Kidney Disease Research, Translational Research Institute, Faulty of Medicine, The University of Queensland at the Princess Alexandra, Brisbane, QLD 4072, Australia"},{"name":"Department of Nephrology, The University of Queensland at Princess Alexandra Hospital, Brisbane, QLD 4102, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8732-7908","authenticated-orcid":false,"given":"Glenda C.","family":"Gobe","sequence":"additional","affiliation":[{"name":"Centre for Kidney Disease Research, Translational Research Institute, Faulty of Medicine, The University of Queensland at the Princess Alexandra, Brisbane, QLD 4072, Australia"},{"name":"School of Biomedical Sciences, Faculty of Medicine, The University of Queensland at the Translational Research Institute, Brisbane, QLD 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5734-2931","authenticated-orcid":false,"given":"David","family":"Nikolic-Paterson","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Monash Medical Centre and Monash University Centre for Inflammatory Diseases, Melbourne, VIC 3168, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David P.","family":"Fairlie","sequence":"additional","affiliation":[{"name":"Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia"},{"name":"Centre for Inflammation and Disease Research, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2856-6650","authenticated-orcid":false,"given":"David A.","family":"Vesey","sequence":"additional","affiliation":[{"name":"Centre for Kidney Disease Research, Translational Research Institute, Faulty of Medicine, The University of Queensland at the Princess Alexandra, Brisbane, QLD 4072, Australia"},{"name":"Department of Nephrology, The University of Queensland at Princess Alexandra Hospital, Brisbane, QLD 4102, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1016\/j.kint.2016.09.010","article-title":"Management of patients with diabetes and CKD: Conclusions from a \u201cKidney Disease: Improving Global Outcomes\u201d (KDIGO) Controversies Conference","volume":"90","author":"Perkovic","year":"2016","journal-title":"Kidney Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/dom.13942","article-title":"Chronic kidney disease in type 2 diabetes: Implications for managing glycaemic control, cardiovascular and renal risk","volume":"22","author":"Stephens","year":"2020","journal-title":"Diabetes Obes. 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