Dysregulation of CXCL1 expression and neutrophil recruitment in insulin resistance and diabetes-related periodontitis in male mice

• DOI: 10.2337/figshare.22596181.v1
• Publication Date: 2023-04-14T17:20:48Z
• Authors: Takanori Shinjo; Satoru Onizuka; Yumi Zaitsu; Atsushi Ishikado; Kyoungmin Park; Qian Li; Hisashi Yokomizo; Tatsuro Zeze; Kohei Sato; Ronald St-Louis; Jialin Fu; Wu I-Hsien; Koji Mizutani; Hatice Hasturk; Thomas E Van Dyke; Fusanori Nishimura; George L King
• Keywords: CXCL1

<p> </p> <p>Insulin resistance and hyperglycemia are risk factors for periodontitis poor wound healing in diabetes, which have been associated with selective loss of insulin- activation the PI3K/Akt pathway gingiva. This study showed that insulin mouse gingiva due to deletion smooth muscle fibroblast receptor (SMIRKO mice) or systemic metabolic changes induced by high fat diet (HFD) HFD-fed mice exacerbated periodontitis-induced alveolar bone loss, preceded delayed neutrophil monocyte recruitment impaired bacterial clearance compared their respective controls. The immunocytokines, CXCL1, CXCL2, MCP-1, TNFα, IL-1β IL-17A exhibited maximal expression male SMIRKO Targeted overexpression CXCL1 adenovirus normalized prevented both models resistance. Mechanistically, enhanced lipopolysaccharide-induced production human gingival fibroblasts (GFs), via Akt NF-κB activation, were reduced GFs from mice. These results provided first report signaling can enhance endotoxin modulate recruitment, suggesting as a new therapeutic direction diabetes.