1. Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China;
2. State Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi'an, 710032, China;
3. Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China;
4. Department of Nephrology, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710032, China.
* These authors (Hong-Bao Liu, Qiu-Hong Meng, De-Wei Du and Ji-Feng Sun) contributed equally to this work.
Bcrp1/ABCG2 is exclusively expressed in side population (SP) cells, however, it has not been fully elucidated whether it has an impact on the viability, proliferation and paracrine actions in kidney SP cells under oxygen-glucose deprivation (OGD) followed by reoxygenation. In this study, we found that 2-h OGD did not injure SP cells (sub-lethal OGD) but induced SP cells proliferation 48 and 72 h after reoxygenation; whereas 4-h OGD markedly injured the cells (lethal OGD) and led to apoptosis 24-72 h after reoxygenation. Fumitremorgin C, an inhibitor of ABCG2, attenuated both the proliferation and viability of SP cells. Sub-lethal and lethal OGD induced the increase in the secretion of vascular endothelial growth factor, insulin-like growth factor 1, hepatocyte growth factor, and stromal cell-derived factor-1α in kidney SP cells, which was inhibited by Fumitremorgin C. Collectively, these findings provide evidence for a crucial role for the ABCG2 expression in the viability, proliferation and paracrine actions of kidney SP cells after OGD.
Keywords: Stem cells, Side population, Kidney, Proliferation, Apoptosis, Paracrine, ischemia, hypoxia, oxygen-glucose deprivation.