Depleted lamin B1: a possible marker of the involvement of senescence in endometriosis?

Malvezzi, Helena; Viana, Bruno Gallani; Dobo, Cristine; Filippi, Renée Zon; Podgaec, Sérgio; Piccinato, Carla de Azevedo

doi:10.1007/s00404-018-4691-y

Cited by 7 publications

(12 citation statements)

References 55 publications

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“…However, between-group comparisons revealed that the levels of SYTOX dead-cell stain fluorescence in EEE and LEE cells that had been treated with rutin + ABE were significantly reduced in comparison with those of EEC cells exposed to the same treatment, indicating that EEE and LEE cells are more resistant to treatment-induced cell death. These results are in accord with a recent report from our research group [34] in which we describe reduced levels of a lamin B1, a protein responsible for cellular apoptosis and senescence, and the presence of apoptosis-resistant cells in endometrial lesions of patients with endometriosis. Since the regulation of the apoptotic process is defective in cells of endometrial lesions, such tissues may not respond to drugs that normally induce cell death in other tissues [23].…”

Section: Discussionsupporting

confidence: 93%

The Effect of Rutin and Extracts of Uncaria guianensis (Aubl.) J. F. Gmeland on Primary Endometriotic Cells: A 2D and 3D Study

et al. 2020

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There is increasing interest in the potential of natural compounds to treat diseases, such as endometriosis, a gynecological disorder that affects 10–15% of women of reproductive age, and it is related to severe pelvic pain and infertility. We have evaluated the in vitro effects of rutin and the aqueous bark, roots, and leaf extracts (ABE, ARE, and ALE, respectively) and isolated components of Uncaria guianensis on stromal cells from eutopic endometrium and lesions of patients with endometriosis. Two- and three-dimensional cultures were used to assess the cell death and production of reactive oxygen species (ROS), cytokines and growth factors of cells following exposure to these natural products. The applied treatments did not reduce cellular viability, but ROS production did increase. In addition, significant increases in the levels of interleukin (IL)-15, IL-17A, IL-4, IL-6, tumor necrosis factor-α, and vascular endothelium growth factor were observed when 2D-cells from endometrium of patients with endometriosis were treated with ABE, while exposure to ALE induced significant increases in epidermal growth factor in lesion cells.

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Section: Discussionsupporting

confidence: 93%

The Effect of Rutin and Extracts of Uncaria guianensis (Aubl.) J. F. Gmeland on Primary Endometriotic Cells: A 2D and 3D Study

et al. 2020

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“…While no specific mutation in the coding sequence of lamin B has been linked to human cardiac diseases, increased expression of lamin B has been reported in peripheral leukocyte as well as in a variant of autosomal dominant leukodystrophy 18 . Overexpression of lamin B has been observed in ataxia telangiectasis 41 and that correcting its levels appears to mitigate nuclear misshaping and premature senescence of patients’ cells 42,43 . These observations suggest that increased expression of lamin B may be detrimental to cells and perturbs the homeostasis of nuclear function as suggested by its irregular shape and size.…”

Section: Discussionmentioning

confidence: 99%

Lamin B is a target for selective nuclear PQC by BAG3: implication for nuclear envelopathies

et al. 2019

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Nuclear envelopathies are recognized genetic disorders affecting individuals with mutations in their genes encoding members of the lamin family of nuclear envelope proteins that are responsible for maintaining the architectural structure of the nucleus. Irregularity in shape and size of the nuclei, nuclear membrane rupture, and appearance of micronuclei in the cytoplasm are among the pathological features of the syndrome. Here, we demonstrate that Bcl2-associated anthanogene-3 (BAG3), a stress-induced co-chaperone protein that by association with heat-shock protein 70 (HSP70) participates in regulation of autophagy, plays a critical role in the integrity of the nuclear membrane in cardiomyocytes. Cells subjected to proteotoxic stress or BAG3 downregulation show perinuclear accumulation of the aberrant ubiquitinated proteins that are often associated with the appearance of misshapen, enlarged, and elongated nuclei. There were dense accumulations of lamin B in the perinuclear area and distribution of lamin B-positive micronuclei in the cytoplasmic space, indicative of nuclear envelope rupture. Overexpression of BAG3 in cells under proteotoxic stress ameliorated pathological nuclear morphology and reduced cytoplasmic distribution of the micronuclei particles. Subcellular co-localization and co-immunoprecipitation demonstrated interaction of lamin B with the BAG domain of BAG3 and HSP70, suggesting the importance of BAG3 in the selective clearance of a surplus of aggregated lamin B that is generated during stress conditions. Our findings define a novel role for BAG3 in nuclear protein quality control and suggest an alternative pathogenetic pathway that contributes to the development of nuclear envelopathies.

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“…In our previous study, we demonstrated a decrease in lamin b1 expression in endometriosis lesions compared to that in the eutopic endometrium; however, we did not consider the different phases of the menstrual cycle [ 29 ]. In this study, in an enlarged subset of patients, we found a difference in lamin b1 expression during the proliferative phase, where lamin b1 concentration was lower in endometriosis lesions than in the eutopic endometrium.…”

Section: Discussionmentioning

confidence: 99%

“…Currently, several biomarkers are used to monitor senescent cells in a given tissue both in vitro and in vivo, such as p16 Ink4a and lamin b1 [ 26 , 27 , 28 ]. Interestingly, we observed a decrease in lamin b1 expression in endometriosis lesions compared to that in the eutopic endometrium [ 29 ]. Moreover, some cytokines known to be present in the SASP, namely IL-6, IL-8, IL-1β, and IL-15 [ 25 , 30 ], which significantly overlap with secreted cytokines related to chronic endometriosis [ 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

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

Malvezzi

Dobo

Filippi

et al. 2022

IJMS

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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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Depleted lamin B1: a possible marker of the involvement of senescence in endometriosis?

Abstract: We observed reduced detection of lamin B1 in the ectopic endometrium raising the possibility that the presence of senescent cells might be contributing to the maintenance and progression of endometriosis by apoptosis resistance and peritoneal stress inherent of the disease.

Cited by 7 publications

References 55 publications

The Effect of Rutin and Extracts of Uncaria guianensis (Aubl.) J. F. Gmeland on Primary Endometriotic Cells: A 2D and 3D Study

The Effect of Rutin and Extracts of Uncaria guianensis (Aubl.) J. F. Gmeland on Primary Endometriotic Cells: A 2D and 3D Study

Lamin B is a target for selective nuclear PQC by BAG3: implication for nuclear envelopathies

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

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