Altered p16Ink4a, IL-1β, and Lamin b1 Protein Expression Suggest Cellular Senescence in Deep Endometriotic Lesions

Helena Malvezzi, Cristine Dobo, Renee Zon Filippi, Renée Zon Filippi, Helen Mendes do Nascimento, Laura Palmieri, Laura Palmieri da Silva E Sousa, Juliana Meola, Carla Azevedo Piccinato, Carla de Azevedo Piccinato, Sérgio Podgaec
International journal of molecular sciences · 2022 · vol. 23(5) , pp. 2476 · doi:10.3390/ijms23052476 · PMID:35269619 · PMC8910415 · W4213420647
article OA: gold CC0 ⤵ 11 in-corpus citations
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This study found increased p16Ink4a and IL-1β expression, along with decreased lamin b1, in deep endometriotic lesions compared to eutopic endometrium, suggesting cellular senescence.

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Abstract

Endometriosis causes immunological and cellular alterations. Endometriosis lesions have lower levels of lamin b1 than the endometrium. Moreover, high levels of pro-inflammatory markers are observed in the peritoneal fluid, follicular fluid, and serum in endometriosis lesions. Thus, we hypothesized that the accumulation of senescent cells in endometriosis tissues would facilitate endometriosis maintenance in an inflammatory microenvironment. To study senescent cell markers and the senescence-associated secretory phenotype (SASP) in endometriosis lesions, we conducted a cross-sectional study with 27 patients undergoing video laparoscopy for endometriosis resection and 19 patients without endometriosis. Endometriosis lesions were collected from patients with endometriosis, while eutopic endometrium was collected from patients both with and without endometriosis. Tissues were evaluated for senescence markers (p16Ink4a, lamin b1, and IL-1β) and interleukin concentrations. The expression of p16Ink4a increased in lesions compared to that in eutopic endometrium from endometriosis patients in the secretory phase. In the proliferative phase, lesions exhibited lower lamin b1 expression but higher IL-4 expression than the eutopic endometrium. Further, IL-1β levels were higher in the lesions than in the eutopic endometrium in both the secretory and proliferative phases. We believe that our findings may provide targets for better therapeutic interventions to alleviate the symptoms of endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometriosis Interleukin-1beta Biomarkers Biomarkers Cellular Senescence Cross-Sectional Studies Cyclin-Dependent Kinase Inhibitor p16 Cyclin-Dependent Kinase Inhibitor p16 Cyclin-Dependent Kinase Inhibitor p16 Endometrium Endometrium Female Humans Interleukin-1beta Lamin Type B

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