PIM2 Promotes the Development of Ovarian Endometriosis by Enhancing Glycolysis and Fibrosis

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This study found that PIM2 promotes ovarian endometriosis development by enhancing glycolysis and fibrosis via PKM2 upregulation, and PIM2 inhibition reduced endometriosis in mice.

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This paper studied the role and mechanism of the kinase PIM2 in ovarian endometriosis, using immunohistochemistry on ovarian endometriosis tissues and mechanistic experiments in endometriotic cells, along with pharmacologic inhibition and in vivo modeling. The authors report that PIM2, glycolysis-related proteins (including HK2 and PKM2), and fibrosis/mesenchymal markers (SMH, Desmin, and α-SMA) are strongly expressed in ovarian endometriosis, and that in endometriotic cells PIM2 enhances glycolysis and fibrosis by upregulating PKM2; treatment with the PIM2 inhibitor SMI-4a and a PIM2 knockout mouse model both inhibited endometriosis development. A key limitation explicitly implied by the study design is that mechanistic evidence relies on specific biomarkers and pathway modulation rather than fully defined upstream drivers or comprehensive pathway mapping. This paper is centrally about endometriosis — it demonstrates that PIM2 promotes ovarian endometriosis by enhancing glycolysis and fibrosis.

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Abstract

Endometriosis is a common gynecological disorder characterized by the presence of the endometrial glands and the stroma outside the uterine cavity. The disease affects reproductive function and quality of life in women of reproductive age. Endometriosis is similar to tumors in some characteristics, such as glycolysis. PIM2 can promote the development of tumors, but the mechanism of PIM2 in endometriosis is still unclear. Therefore, our goal is to study the mechanism of PIM2 in endometriosis. Through immunohistochemistry, we found PIM2, HK2, PKM2, SMH (smooth muscle myosin heavy chain), Desmin, and α-SMA (α-smooth muscle actin) were strongly expressed in the ovarian endometriosis. In endometriotic cells, PIM2 enhanced glycolysis and fibrosis via upregulating the expression of PKM2. Moreover, the PIM2 inhibitor SMI-4a inhibited the development of endometriosis. And we established a PIM2 knockout mouse model of endometriosis to demonstrate the role of PIM2 in vivo. In summary, our study indicates that PIM2 promotes the development of endometriosis. PIM2 may serve as a promising therapeutic target for endometriosis.
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Abstract

Endometriosis is a common gynecological disorder characterized by the presence of the endometrial glands and the stroma outside the uterine cavity. The disease affects reproductive function and quality of life in women of reproductive age. Endometriosis is similar to tumors in some characteristics, such as glycolysis. PIM2 can promote the development of tumors, but the mechanism of PIM2 in endometriosis is still unclear. Therefore, our goal is to study the mechanism of PIM2 in endometriosis. Through immunohistochemistry, we found PIM2, HK2, PKM2, SMH (smooth muscle myosin heavy chain), Desmin, and α-SMA (α-smooth muscle actin) were strongly expressed in the ovarian endometriosis. In endometriotic cells, PIM2 enhanced glycolysis and fibrosis via upregulating the expression of PKM2. Moreover, the PIM2 inhibitor SMI-4a inhibited the development of endometriosis. And we established a PIM2 knockout mouse model of endometriosis to demonstrate the role of PIM2 in vivo. In summary, our study indicates that PIM2 promotes the development of endometriosis. PIM2 may serve as a promising therapeutic target for endometriosis. Similar content being viewed by others Data Availability The data underlying this article will be shared at reasonable request to the corresponding author. Code Availability Not applicable.

References

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ZY and TY supervised the study. MW and TY wrote and edited the manuscript with feedback from all authors. Corresponding authors Ethics declarations Ethics Approval Human Investigation Ethical Committee of Affiliated Hospital of Weifang Medical University approved this study (approved No. Wyfy-2022-ky-094). Consent to Participate Informed consent was obtained from all patients for being included in the study. Consent for Publication All authors consent to the publication of the article. Conflict of Interest The authors declare no competing interests. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information Below is the link to the electronic supplementary material. Supplementary Table S1 (download DOCX ) (DOCX 12 kb) Supplementary Table S2 (download DOCX ) (DOCX 11 kb) Supplementary Fig. 1 (download PNG ) The diagram of animal experiment procedure. (PNG 4673 kb) Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Wang, M., Fan, R., Jiang, J. et al. PIM2 Promotes the Development of Ovarian Endometriosis by Enhancing Glycolysis and Fibrosis. Reprod. Sci. 30, 2692–2702 (2023). https://doi.org/10.1007/s43032-023-01208-w Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-023-01208-w

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Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis

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