Interplay between autophagy and NLRP3 inflammasome in the gingival mucosa of estrogen‐deficient and streptozotocin‐induced diabetic rats

This study investigated how estrogen deficiency and streptozotocin-induced diabetes mellitus (DM) affect rat gingival mucosa, focusing on autophagy and NLRP3 inflammasome expression. Twenty rats were ovariectomized (OVX) or SHAM-operated (SHAM) and divided into SHAM, OVX, SHAM-DM, and OVX-DM groups. After 7 weeks, rats were euthanized, and maxillae containing gingival mucosa were processed for histology and immunohistochemistry for autophagy (Beclin-1, LC3B) and inflammasome (NLRP3, IL-1β) markers. Publicly available data were analyzed to assess these markers in gingival tissue from periodontitis patients. Epithelial and stratum corneum thickness increased in OVX, SHAM-DM, and OVX-DM groups. SHAM-DM and OVX-DM rats showed more keratinocytes with large vesicular nuclei and prominent nucleoli. The highest numbers of mast cells, especially degranulated ones, occurred in OVX-DM. Increased Beclin-1, LC3B, NLRP3, and IL-1β expression was detected in the lamina propria and gingival epithelium, particularly in OVX-DM. These markers showed positive correlations. Bioinformatics revealed increased LC3B, NLRP3, and IL1B transcription in periodontitis patients' gingiva. Positive correlations were found between BECN1 and LC3B, BECN1 and NLRP3, LC3B and NLRP3, and NLRP3 and IL1B; BECN1 and IL1B correlated negatively. These findings suggest that increased autophagy and NLRP3 inflammasome activation contribute to gingival mucosa damage in estrogen-deficient diabetic rats and in periodontitis patients.