Renal subcapsular delivery of PGE₂ promotes kidney repair by activating endogenous Sox9⁺ stem cells.

ABSTRACT: Prostaglandin E₂ (PGE₂) has recently been recognized to play a role in immune regulation and tissue regeneration. However, the short half-life of PGE₂ limits its clinical application. Improving the delivery of PGE₂ specifically 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, PGE₂ exhibits 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 PGE₂ could 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.

SUBMITTER: Chen S 

PROVIDER: S-EPMC8554536 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature