Kidney-resident macrophages promote a proangiogenic environment in the normal and chronically ischemic mouse kidney

Amrutesh S. Puranik, Irina A. Leaf, Mark A. Jensen, Ahmad F. Hedayat, Ahmad Saad, Ki Wook Kim, Abdulrahman M. Saadalla, John R. Woollard, Sonu Kashyap, Stephen C. Textor, Joseph P. Grande, Amir Lerman, Robert D. Simari, Gwendalyn J. Randolph, Jeremy S. Duffield, Lilach O. Lerman

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Renal artery stenosis (RAS) caused by narrowing of arteries is characterized by microvascular damage. Macrophages are implicated in repair and injury, but the specific populations responsible for these divergent roles have not been identified. Here, we characterized murine kidney F4/80+CD64+ macrophages in three transcriptionally unique populations. Using fate-mapping and parabiosis studies, we demonstrate that CD11b/cint are long-lived kidney-resident (KRM) while CD11chiMϕ, CD11cloMϕ are monocyte-derived macrophages. In a murine model of RAS, KRM self-renewed, while CD11chiMϕ and CD11cloMϕ increased significantly, which was associated with loss of peritubular capillaries. Replacing the native KRM with monocyte-derived KRM using liposomal clodronate and bone marrow transplantation followed by RAS, amplified loss of peritubular capillaries. To further elucidate the nature of interactions between KRM and peritubular endothelial cells, we performed RNA-sequencing on flow-sorted macrophages from Sham and RAS kidneys. KRM showed a prominent activation pattern in RAS with significant enrichment in reparative pathways, like angiogenesis and wound healing. In culture, KRM increased proliferation of renal peritubular endothelial cells implying direct pro-angiogenic properties. Human homologs of KRM identified as CD11bintCD11cintCD68+ increased in post-stenotic kidney biopsies from RAS patients compared to healthy human kidneys, and inversely correlated to kidney function. Thus, KRM may play protective roles in stenotic kidney injury through expansion and upregulation of pro-angiogenic pathways.

Original languageEnglish (US)
Article number13948
JournalScientific reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

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    Puranik, A. S., Leaf, I. A., Jensen, M. A., Hedayat, A. F., Saad, A., Kim, K. W., Saadalla, A. M., Woollard, J. R., Kashyap, S., Textor, S. C., Grande, J. P., Lerman, A., Simari, R. D., Randolph, G. J., Duffield, J. S., & Lerman, L. O. (2018). Kidney-resident macrophages promote a proangiogenic environment in the normal and chronically ischemic mouse kidney. Scientific reports, 8(1), [13948]. https://doi.org/10.1038/s41598-018-31887-4