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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Cellular Endocrinology
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1375771

Smoothelin-like protein 1 promotes insulin sensitivity and modulates the contractile properties of endometrial epithelial cells with insulin resistance

Provisionally accepted
Ilka Keller Ilka Keller 1,2Ádám Ungvári Ádám Ungvári 1Richárd Kinter Richárd Kinter 1Fanni Szalmás Fanni Szalmás 1Endre Kókai Endre Kókai 1Beata Lontay Beata Lontay 1*
  • 1 Department of Medical Chemistry, Faculty of Medicinie, University of Debrecen, Debrecen, Hungary
  • 2 Doctoral School of Molecular Medicine, University of Debrecen, Debrecen, Hajdu-Bihar, Hungary

The final, formatted version of the article will be published soon.

    The incidence of infertility is significantly higher in women with diseases linked to impaired glucose homeostasis, such as insulin resistance. Defective glucose metabolism interferes with fertilization; however, the molecular mechanism underlying this interference is unclear.Smoothelin-like protein 1 (SMTNL1) was isolated from muscle and steroid hormone-responsive tissues and regulates the contractile functions of various cell types through the inhibition of myosin phosphatase (MP) holoenzyme. In addition, SMTNL-1 after phosphorylation at Ser301 by protein kinase A translocates to the nucleus and functions as a transcriptional co-activator of the progesterone receptor-B. SMTNL1 null mice exhibit reduced reproductive fitness and are more prone to type 2 diabetes mellitus. However, the role of SMTNL1 in endometrial epithelial cells is not known. We show that SMTNL1 promotes the differentiation of endometrial epithelial cells in a progesterone-dependent manner to attenuate insulin resistance. Furthermore, SMTNL1 hampers the migration capacity of epithelial cells in a gestational diabetes model by inhibiting the expression of MYPT1, the regulatory subunit of MP, and the activity of the holoenzyme, resulting in increased phosphorylation of the 20 kDa regulatory myosin light chain. SMTNL1 also acts as an insulin-sensitizing agent by increasing the gene expression of PP2A and DUPS9 protein phosphatases, resulting in decreased ERK1/2 activity and, hence, decreasing the phosphorylation of IRS-1 at Ser612 under gestational diabetes conditions. In conclusion, SMTNL1 may have therapeutic relevance to the progesterone-dependent inhibition of endometrial epithelial cell migration under hyperglycemic conditions and insulin sensitivity in the endometrium in gestational diabetes or other metabolic disorders.

    Keywords: Endometrium, Insulin Resistance, insulin signaling, Migration, Gene Expression

    Received: 24 Jan 2024; Accepted: 10 May 2024.

    Copyright: © 2024 Keller, Ungvári, Kinter, Szalmás, Kókai and Lontay. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Beata Lontay, Department of Medical Chemistry, Faculty of Medicinie, University of Debrecen, Debrecen, 4032, Hungary

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