Expression of Protein Markers of Adipogenesis in Endometriotic Lesions

In: Cell and Tissue Biology · 2020 · vol. 14(2) , pp. 129–138 · doi:10.1134/s1990519x20020066 · W3016548229
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This study found that endometriotic lesions and underlying peritoneum express high levels of adipogenesis markers (FABP4, PLA2G2A, ADH1B, C7), suggesting a role for adipogenic stem cells in endometriosis pathogenesis.

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The study examined expression of adipogenesis-associated protein markers—C7, FABP4, ADH1B, and PLA2G2A—in endometriotic lesions and peritoneal tissue by comparing ectopic versus eutopic endometrium, then validating findings using real-time PCR and immunohistochemistry in peritoneal samples from patients with endometriosis and healthy controls. The authors found that high expression of these genes was attributable to endometriotic lesions and peritoneal cells rather than eutopic endometrium, with expression differences reported as roughly 200–300-fold in prior data and confirmed by the performed validation assays. They interpret similarly high expression in endometriotic nodules and adjacent peritoneum as consistent with a common origin, supporting the metaplastic theory, and propose adipogenic stem cells as potentially involved in pathogenesis, while noting the evidence is based on expression rather than direct mechanistic demonstration. This paper is centrally about endometriosis — specifically, it assesses adipogenesis marker genes/proteins (C7, FABP4, ADH1B, PLA2G2A) expressed in endometriotic lesions and surrounding peritoneum.

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Abstract

Endometriosis is a widespread disorder in which a tissue morphologically and physiologically similar to endometrium is observed outside the uterine cavity. Earlier, we identified a number of genes that are overexpressed in ectopic endometrium compared to eutopic endometrium. C7, FABP4, ADH1B, and PLA2G2A were the most expressed genes. The difference in their expression level was 200–300 times higher. In this work, we verified the results using real-time PCR and immunohistochemistry and examined the expression of these genes in the peritoneum of patients with endometriosis and healthy women. We have shown that a high level of expression of these genes is due to endometriotic lesions and peritoneal cells rather than eutopic endometrium. The proteins encoded by these genes (FABP4, PLA2G2A, and ADH1B) are known to be adipogenesis markers. Protein C7 is also involved in the differentiation of adipose stem cells. The equally high level of expression of these genes in endometriosis nodules and underlying peritoneum may point to a common origin of these tissues, which supports the metaplastic theory of the origin of endometriosis. In addition, our data can be interpreted as an indication that adipogenic stem cells may play a role in the pathogenesis of endometriosis. Also, our data can be interpreted as an indication of a possible involvement of adipogenic stem cells in the pathogenesis of endometriosis.
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Abstract

Endometriosis is a widespread disorder in which a tissue morphologically and physiologically similar to endometrium is observed outside the uterine cavity. Earlier, we identified a number of genes that are overexpressed in ectopic endometrium compared to eutopic endometrium. C7, FABP4, ADH1B, and PLA2G2A were the most expressed genes. The difference in their expression level was 200–300 times higher. In this work, we verified the results using real-time PCR and immunohistochemistry and examined the expression of these genes in the peritoneum of patients with endometriosis and healthy women. We have shown that a high level of expression of these genes is due to endometriotic lesions and peritoneal cells rather than eutopic endometrium. The proteins encoded by these genes (FABP4, PLA2G2A, and ADH1B) are known to be adipogenesis markers. Protein C7 is also involved in the differentiation of adipose stem cells. The equally high level of expression of these genes in endometriosis nodules and underlying peritoneum may point to a common origin of these tissues, which supports the metaplastic theory of the origin of endometriosis. In addition, our data can be interpreted as an indication that adipogenic stem cells may play a role in the pathogenesis of endometriosis. Also, our data can be interpreted as an indication of a possible involvement of adipogenic stem cells in the pathogenesis of endometriosis. Similar content being viewed by others

References

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Endocrinol., 2018, vol. 9, p. 644. https://doi.org/10.3389/fendo.2018.00644 Yarmolinskaya, M.I. and Ailamazyan, E.K., Genital’nyi endometrioz. Razlichnye grani problemy (Genital Endometriosis: Various Facets of the Problem), St. Petersburg: Eko-Vektor, 2017. Ying, L., Zhang, F., Pan, X., Chen, K., Zhang, N., Jin, J., Wu, J., Feng, J., Yu, H., Jin, H., and Su, D., Complement component 7 (C7), a potential tumor suppressor, is correlated with tumor progression and prognosis, Oncotarget, 2016, vol. 7, pp. 86536–86546. Funding This work was supported by the Russian Science Foundation, project no. 19-15-00108. Author information Authors and Affiliations Corresponding author Ethics declarations Conflict of interest. The authors declare that they have no conflict of interest. Statement of compliance with standards of research involving humans as subjects. All procedures performed with the participation of people complied with the ethical standards of the institutional and/or national research ethics committee and the Helsinki Declaration (1964) and its subsequent changes or comparable to ethical standards. Informed consent was obtained from each participant. The work was approved by the Ethics Committee of the Ott Research Institute of Obstetrics, Gynecology, and Reproductology, Additional information Translated by I. Fridlyanskaya Abbreviations: IHC—immunohistochemistry, EGE—external genital endometriosis, RT-PCR—reverse transcription polymerase chain reaction, EH—endometrioid heterotopias, FDR—false discovery rate, average proportion of false hypotheses. Rights and permissions About this article Cite this article Malysheva, O.V., Kopteva, O.S., Krylova, Y.S. et al. Expression of Protein Markers of Adipogenesis in Endometriotic Lesions. Cell Tiss. Biol. 14, 129–138 (2020). https://doi.org/10.1134/S1990519X20020066 Received: Revised: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1134/S1990519X20020066

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