摘要：SummaryProstaglandin E2(PGE2) has recently been recognized to play a role in immune regulation and tissue regeneration. However, the short half-life of PGE2limits its clinical application. Improving the delivery of PGE2specifically to the target organ with a prolonged release method is highly desirable. Taking advantage of the adequate space and proximity of the renal parenchyma, renal subcapsular delivery allows minimally invasive and effective delivery to the entire kidney. Here, we report that by covalently cross-linking it to a collagen matrix, PGE2exhibits an adequate long-term presence in the kidney with extensive intraparenchymal penetration through renal subcapsular delivery and significantly improves kidney function. Sox9 cell lineage tracing with intravital microscopy revealed that PGE2could activate the endogenous renal progenitor Sox9+cells through the Yap signaling pathway. Our results highlight the prospects of utilizing renal subcapsular-based drug delivery and facilitate new applications of PGE2-releasing matrices for regenerative therapy.Graphical abstractDisplay OmittedHighlights•PGE2exhibits an adequate long-term release by being covalently cross-linked to collagen•The renal subcapsular space serves as a reservoir for the delivery of PGE2•Sox9+renal progenitor cells can be lineage traced intravitally by microscopy•PGE2activates the endogenous renal progenitor Sox9+cells through the YAP pathwayDrug delivery system; Pathophysiology; Cell biology; Stem cells research
