{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:13:23Z","timestamp":1790014403959,"version":"4.0.1"},"reference-count":66,"publisher":"American Physiological Society","issue":"6","funder":[{"name":"Sapporo Medical University","award":["Grants for Research and Education 2015 and 2016"],"award-info":[{"award-number":["Grants for Research and Education 2015 and 2016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2017,12,1]]},"abstract":"<jats:p> Acute kidney injury (AKI) after acute myocardial infarction (MI) worsens the prognosis of MI patients. Although type 2 diabetes mellitus (DM) is a major risk factor of AKI after MI, the underlying mechanism remains unclear. Here, we examined the roles of renal Toll-like receptors (TLRs) in the impact of DM on AKI after MI. MI was induced by coronary artery ligation in Otsuka-Long-Evans-Tokushima fatty (OLETF) rats, a rat DM model, and Long-Evans-Tokushima-Otsuka (LETO) rats, nondiabetic controls. Sham-operated rats served as no-MI controls. Renal mRNA levels of TLR2 and myeloid differentiation factor 88 (MyD88) were significantly higher in sham-operated OLETF rats than in sham-operated LETO rats, although levels of TLR1, TLR3, and TLR4 were similar. At 12 h after MI, protein levels of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in the kidney were elevated by 5.3- and 4.0-fold, respectively, and their mRNA levels were increased in OLETF but not LETO rats. The increased KIM-1 and NGAL expression levels after MI in the OLETF kidney were associated with upregulated expression of TLR1, TLR2, TLR4, MyD88, IL-6, TNF-\u03b1, chemokine (C-C motif) ligand 2, and transforming growth factor-\u03b2<jats:sub>1<\/jats:sub> and also with activation of p38 MAPK, JNK, and NF-\u03baB. Cu-CPT22, a TLR1\/TLR2 antagonist, administered before MI significantly suppressed MI-induced upregulation of KIM-1, TLR2, TLR4, MyD88, and chemokine (C-C motif) ligand 2 levels and activation of NF-\u03baB, whereas NGAL levels and IL-6 and TNF-\u03b1 expression levels were unchanged. The results suggest that DM increases the susceptibility to AKI after acute MI by augmented activation of renal TLRs and that TLR1\/TLR2-mediated signaling mediates KIM-1 upregulation after MI. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY This is the first report to demonstrate the involvement of Toll-like recpetors (TLRs) in diabetes-induced susceptibility to acute kidney injury after acute myocardial infarction. We propose that the TLR1\/TLR2 heterodimer may be a new therapeutic target for the prevention of acute kidney injury in diabetic patients. <\/jats:p>","DOI":"10.1152\/ajpheart.00205.2017","type":"journal-article","created":{"date-parts":[[2017,8,20]],"date-time":"2017-08-20T00:30:25Z","timestamp":1503189025000},"page":"H1130-H1142","source":"Crossref","is-referenced-by-count":26,"title":["Diabetes increases the susceptibility to acute kidney injury after myocardial infarction through augmented activation of renal Toll-like receptors in rats"],"prefix":"10.1152","volume":"313","author":[{"given":"Kouhei","family":"Ohno","sequence":"first","affiliation":[{"name":"Department of Cardiovascular, Renal, and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Kuno","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular, Renal, and Metabolic Medicine, Sapporo 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