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Progenitor Renin Lineage Cells are not involved in the regeneration of glomerular
endothelial cells during experimental renal thrombotic microangiopathy
#MMPMID29771991
Ruhnke L
; Sradnick J
; Al-Mekhlafi M
; Gerlach M
; Gembardt F
; Hohenstein B
; Todorov VT
; Hugo C
PLoS One
2018[]; 13
(5
): e0196752
PMID29771991
show ga
Endothelial cells (EC) frequently undergo primary or secondary injury during
kidney disease such as thrombotic microangiopathy or glomerulonephritis. Renin
Lineage Cells (RLCs) serve as a progenitor cell niche after glomerular damage in
the adult kidney. However, it is not clear whether RLCs also contribute to
endothelial replenishment in the glomerulus following endothelial injury.
Therefore, we investigated the role of RLCs as a potential progenitor niche for
glomerular endothelial regeneration. We used an inducible tet-on
triple-transgenic reporter strain mRen-rtTAm2/LC1/LacZ to pulse-label the
renin-producing RLCs in adult mice. Unilateral kidney EC damage (EC model) was
induced by renal artery perfusion with concanavalin/anti-concanavalin. In this
model glomerular EC injury and depletion developed within 1 day while
regeneration occurred after 7 days. LacZ-labelled RLCs were restricted to the
juxtaglomerular compartment of the afferent arterioles at baseline conditions. In
contrast, during the regenerative phase of the EC model (day 7) a subset of
LacZ-tagged RLCs migrated to the glomerular tuft. Intraglomerular RLCs did not
express renin anymore and did not stain for glomerular endothelial or podocyte
cell markers, but for the mesangial cell markers ?8-integrin and PDGFR?.
Accordingly, we found pronounced mesangial cell damage parallel to the
endothelial injury induced by the EC model. These results demonstrated that in
our EC model RLCs are not involved in endothelial regeneration. Rather,
recruitment of RLCs seems to be specific for the repair of the concomitantly
damaged mesangium.