The Function of SDF-1-CXCR4 Axis in SP Cells-Mediated Protective Role for Renal Ischemia/Reperfusion Injury by SHH/GLI1-ABCG2 Pathway

摘要: Renal ischemia-reperfusion (I/R) injury ranks as the primary cause of acute renal with severe morbidity and mortality. Side population (SP) cells have recently drawn increasing attention due to their critical role in repair regeneration. Unfortunately, underlying mechanism involved I/R remains poorly elucidated. Here, pronounced increases stromal cell-derived factor-1 (SDF-1) its receptor CXC chemokine 4 (CXCR4) were substantiated kidneys from C57BL/6 mice subjected clamp bilateral pedicles mimic ischemia. Similar up-regulation them was also determined SP upon simulated ischemia/reperfusion (SI/R). In contrast non-SP cells, exhibited higher viability, apoptosis resistance, chemotaxis, paracrine actions following SI/R treatment, these further enhanced after SDF-1 stimulation. Interestingly, blocking CXCR4 signaling AMD3100 notably ameliorated above effects. Mechanism analysis corroborated that SDF-1/CXCR4 induced expression ATP-binding cassette transporter ABCG2, an essential element for SP-mediated kidney regeneration injury. Moreover, pretreatment strikingly attenuated ABCG2 elevation cells. Additionally, sonic hedgehog (SHH)-Gli 1 SDF-1/CXCR4-mediated expression. When pretreated intravenously injected into mice, cell-mediated decreases blood urea nitrogen, serum creatinine, histological score noticeably attenuated, indicating pathway mitigated therapeutic function Together, this research suggests axis might act, via Shh-Gli1-ABCG2 signaling, a positive regulator cell-based therapies by Shh-Gli 1-ABCG2 signaling.