MO_III_L: Molecular Sciences III. Lectures
Ilka Keller M.D. 1, Dr. Lontay Beáta1, Dr. Horváth Dániel1, Evelin Major1
1 University of Debrecen, Faculty of Medicine, Department of Medical Chemistry
The incidence of infertility is significantly higher in women who display a history of diseases linked to impaired glucose homeostasis, such as insulin resistance. The insufficiency of glucose metabolism is proved to interfere with the process of healthy reproduction, however, the molecular mechanism of the underlying causes are yet to be uncovered.
Smoothelin-like protein-1 (SMTNL-1) was identified in muscle and steroid hormone-responsive tissues. SMTNL-1 regulates muscle contraction and the cytoskeletal elements of various cells through the inhibition of myosin phosphatase holoenzyme. Also upon phosphorylation at Ser301 by protein kinase A, SMTNL-1 translocates to the nucleus where it could function as a transcriptional regulator of the progesterone receptor-B. Moreover, SMTNL-1 null mice exhibited a generally impaired reproductive fitness, with decreased litter size, also the genetically modified animals were more prone to exhibit metabolic syndrome along with type 2 diabetes mellitus.
In our study, we investigated the effects of SMTNL-1 on the insulin signaling pathway applying Ishikawa cells (representing human endometrial epithelial cells), establishing control, pregnant (PG), and gestational diabetic (GD) models.
To verify the role of SMTNL-1 in the reproductive processes, SMTNL-1 was overexpressed, then the migration was examined by wound healing scratch assay. Several members of the insulin signaling pathway was investigated with semi quantitative western blot analysis.
SMTNL-1 overexpression evoked controversial effect on the migration capacity on a progesterone-dependent manner. SMTNL-1 had no significant effect on the gene expression of the element of insulin signaling pathway, namely IRS-1, Akt and ERK1/2 but their phosphorylation levels were altered. It collectively suggests the insulin-sensitizing effect of SMTNL-1 in epithelial cells and a potential target to improve fertility disorders.
This work was supported by grants from the National Research, Development and Innovation Office (FK125043,
Debrecen University Faculty of Medicine, Doctoral School of Molecular Medicine