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Acute kidney injury (AKI) is a significant condition or complication associated with a high mortality rate. Furthermore, an increasing body of research has revealed that a substantial proportion of AKI patients go on to develop chronic kidney disease and eventually progress to end-stage renal disease (ESRD) in the course of follow-up. On the other hand, pericytes are mesenchyme-derived perivascular cells and represent the primary source of myofibroblasts in animal models of ischemia- reperfusion injury (IRI). CXCL12 is a factor that has been documented to attract bone marrow-derived stem cells during organ injury. Therefore, our hypothesis is that CXCL12 produced by pericytes may have a beneficial effect in the context of AKI.
Ischemia-reperfusion injury (IRI) was employed as the model for AKI. To inhibit pericytes, we administered a specific antibody targeting platelet-derived growth factor receptor β (PDGFRβ) after inducing AKI in C57BL/6 mice. Furthermore, before subjecting the mice to IRI, we conditionally knocked out CXCL12/SDF-1 specifically in pericytes using the Gli1CreERT2/+;Cxcl12F/F model.
The administration of the anti-PDGFRβ antibody resulted in a delayed renal functional recovery in mice on the fifth day after AKI was induced by IRI. Additionally, we demonstrated that CXCL12 was primarily secreted by pericytes, and its receptor CXCR4 was expressed on tubular cells during IRI, as shown by in situ hybridization. The secretion of CXCL12 from pericytes increased following IRI-induced AKI. When the knockout of CXCL12 was performed before IRI, renal microvascular rarefaction was observed after AKI, and the recovery of renal function was impaired. Furthermore, there was a decrease in renal tubular cell proliferation and an increase in apoptosis.
In conclusion, these findings illustrate that pericytes play a role in renal repair following IRI-induced AKI, and it is mainly from pericytes that CXCL12 is secreted, contributing to the beneficial aspect of renal recovery after IRI-induced AKI