Homeobox B4 gene expression is upregulated by ghrelin through PI3-kinase signaling pathway in rat’s bone marrow stromal cells

Year, pages: 2019, 65 - 70

Objective. Ghrelin, a 28 amino acid peptide, has diverse physiological roles. Phosphatidylinositol-bisphosphate 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) are involved in some of the recognized actions of ghrelin. It has been shown that ghrelin upregulates HOXB4 gene expression but the real mechanism of this effect is not clear. Methods. Rat bone marrow stromal cells (BMSCs) were cultured in DMEM. BMSCs were treated with ghrelin (100 μM) for 48 h. Real-time PCR for HOXB4 was performed from Control (untreated BMSCs), BG (BMSCs treated with 100 μM ghrelin), PD (BMSCs treated with 10 μM PD98059, a potent inhibitor of mitogen-activated protein kinase, and 100 μM ghrelin), LY (BMSCs treated with 10 μM LY294002, a strong inhibitor of phosphoinositide 3-kinase, and 100 μM ghrelin) and SY (BMSCs treated with 10 μM LY294002 plus 10 μM PD98059 , and 100 μM ghrelin) groups. Relative gene expression changes were determined using Relative expression software tool 9 (REST 9). Results. HOXB4 gene has been overexpressed in ghrelin-treated BMSCs (p<0.05). PI3K inhibition by LY294002 significantly downregulated the ghrelin-induced overexpression of HOXB4 (p<0.05). Conclusion. We can conclude that ghrelin, through PI3K/Akt pathway, may improve BMSC transplantation potency by reducing its apoptosis. Moreover, upregulating HOXB4 in BMSC and its possible differentiation to HSCs might in the future open the doors to new treatment for hematologic disorders. Therefore, activating the PI3K/Akt pathway, instead of using a non-specific inducer, could be the principal point to increase the efficiency of BMSC-based cell therapies in the future.

Taherkhani, S., Moradi, F., Hosseini, M., Alipour, M., Feizi, H. 2019. Homeobox B4 gene expression is upregulated by ghrelin through PI3-kinase signaling pathway in rat’s bone marrow stromal cells. In ENDOCRINE REGULATIONS, vol. 53, no.2, pp. 65-70. 1210-0668. DOI: https://doi.org/10.2478/enr-2019-0008

Taherkhani, S., Moradi, F., Hosseini, M., Alipour, M., Feizi, H. (2019). Homeobox B4 gene expression is upregulated by ghrelin through PI3-kinase signaling pathway in rat’s bone marrow stromal cells. ENDOCRINE REGULATIONS, 53(2), 65-70. 1210-0668. DOI: https://doi.org/10.2478/enr-2019-0008

Publisher: Sciendo