PMID- 37025887 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230411 IS - 2405-8440 (Print) IS - 2405-8440 (Electronic) IS - 2405-8440 (Linking) VI - 9 IP - 4 DP - 2023 Apr TI - AGEs-RAGE-K(Ca)3.1 pathway mediates palmitic acid-induced migration of PBMCs from patients with type 2 diabetes. PG - e14823 LID - 10.1016/j.heliyon.2023.e14823 [doi] LID - e14823 AB - Type 2 diabetes mellitus (T2DM) is characterized by chronic low-grade systemic inflammation. Tissue infiltration by monocyte migration contributes to the pathogenesis of vascular complications in T2DM. We studied the role of intermediate-conductance Ca(2+)-activated K(+) (K(Ca)3.1) channels in the palmitic acid (PA)-induced migration of peripheral blood mononuclear cells (PBMCs) from T2DM patients and the influence of advanced glycation endproducts (AGEs). A total of 49 T2DM patients and 33 healthy subjects was recruited into this study. Using flow cytometry and Western blotting analysis as well as cell migration assay, we found that there was a significant decrease in frequency of T lymphocytes and monocytes in CD45(+) leukocyte population. PA at 100 muM stimulated migration of PBMCs from T2DM individuals, which was inhibited by the specific K(Ca)3.1 channel blocker TRAM-34 (1 muM). The PBMC migration was positively correlated with glycosylated hemoglobin A1 chain (HbA1c) level of T2DM patients, an indicator of AGEs, and PBMCs with higher level of HbA1c showed upregulated expression of toll-like receptor (TLR) 2/4 and K(Ca)3.1 channels. In THP-1 cells, AGEs at 200 mug/ml increased protein expression of TLR 2/4 and K(Ca)3.1 channels, and were synergistically involved in PA-induced migration through receptors of AGEs (RAGE)-mediated K(Ca)3.1 upregulation. In conclusion, in PBMCs of T2DM patients, AGEs promotes PA-induced migration via upregulation of TLR2/4 and K(Ca)3.1 channels. CI - (c)2023PublishedbyElsevierLtd. FAU - Zhang, Yi AU - Zhang Y AD - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, Shaanxi, China. FAU - Ma, Xiao-Zhen AU - Ma XZ AD - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, Shaanxi, China. FAU - Zhao, Xin-Yi AU - Zhao XY AD - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, Shaanxi, China. FAU - Li, Jing-Jing AU - Li JJ AD - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, Shaanxi, China. FAU - Ma, Shan AU - Ma S AD - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, Shaanxi, China. AD - Department of Endocrinology, The Second Affiliated Hospital, Xi'an Jiaotong University, 157 Fifth West Road, Xi'an, 710004, Shaanxi, China. FAU - Pang, Zheng-Da AU - Pang ZD AD - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, Shaanxi, China. FAU - Xu, Jing AU - Xu J AD - Department of Endocrinology, The Second Affiliated Hospital, Xi'an Jiaotong University, 157 Fifth West Road, Xi'an, 710004, Shaanxi, China. FAU - Du, Xiao-Jun AU - Du XJ AD - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, Shaanxi, China. FAU - Deng, Xiu-Ling AU - Deng XL AD - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, Shaanxi, China. FAU - Wang, Jun-Hong AU - Wang JH AD - Department of Endocrinology, The Second Affiliated Hospital, Xi'an Jiaotong University, 157 Fifth West Road, Xi'an, 710004, Shaanxi, China. AD - Department of Endocrinology, Gongli Hospital, Pudong New Area, Shanghai, 200135, China. LA - eng PT - Journal Article DEP - 20230324 PL - England TA - Heliyon JT - Heliyon JID - 101672560 PMC - PMC10070889 OTO - NOTNLM OT - HbA1c OT - Migration OT - Palmitic acid OT - Peripheral blood mononuclear cells OT - Type 2 diabetes mellitus COIS- The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/04/08 06:00 MHDA- 2023/04/08 06:01 PMCR- 2023/03/24 CRDT- 2023/04/07 02:35 PHST- 2022/09/03 00:00 [received] PHST- 2023/03/08 00:00 [revised] PHST- 2023/03/17 00:00 [accepted] PHST- 2023/04/08 06:01 [medline] PHST- 2023/04/07 02:35 [entrez] PHST- 2023/04/08 06:00 [pubmed] PHST- 2023/03/24 00:00 [pmc-release] AID - S2405-8440(23)02030-3 [pii] AID - e14823 [pii] AID - 10.1016/j.heliyon.2023.e14823 [doi] PST - epublish SO - Heliyon. 2023 Mar 24;9(4):e14823. doi: 10.1016/j.heliyon.2023.e14823. eCollection 2023 Apr.