Gli1+ Pericyte Loss Induces Capillary Rarefaction and Proximal Tubular Injury
- PMID: 27624490
- PMCID: PMC5328159
- DOI: 10.1681/ASN.2016030297
Gli1+ Pericyte Loss Induces Capillary Rarefaction and Proximal Tubular Injury
Abstract
Peritubular capillary rarefaction is hypothesized to contribute to the increased risk of future CKD after AKI. Here, we directly tested the role of Gli1+ kidney pericytes in the maintenance of peritubular capillary health, and the consequences of pericyte loss during injury. Using bigenic Gli1-CreERt2; R26tdTomato reporter mice, we observed increased distance between Gli1+ pericytes and endothelial cells after AKI (mean±SEM: 3.3±0.1 µm before injury versus 12.5±0.2 µm after injury; P<0.001). Using a genetic ablation model, we asked whether pericyte loss alone is sufficient for capillary destabilization. Ten days after pericyte ablation, we observed endothelial cell damage by electron microscopy. Furthermore, pericyte loss led to significantly reduced capillary number at later time points (mean±SEM capillaries/high-power field: 67.6±4.7 in control versus 44.1±4.8 at 56 days; P<0.05) and increased cross-sectional area (mean±SEM: 21.9±0.4 µm2 in control versus 24.1±0.6 µm2 at 10 days; P<0.01 and 24.6±0.6 µm2 at 56 days; P<0.001). Pericyte ablation also led to hypoxic focal and subclinical tubular injury, reflected by transient expression of Kim1 and vimentin in scattered proximal tubule segments. This analysis provides direct evidence that AKI causes pericyte detachment from capillaries, and that pericyte loss is sufficient to trigger transient tubular injury and permanent peritubular capillary rarefaction.
Keywords: AKI; CKD; capillary; pericyte.
Copyright © 2017 by the American Society of Nephrology.
Figures
![Figure 1.](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/5328159/bin/ASN.2016030297f1.gif)
![Figure 2.](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/5328159/bin/ASN.2016030297f2.gif)
![Figure 3.](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/5328159/bin/ASN.2016030297f3.gif)
![Figure 4.](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/5328159/bin/ASN.2016030297f4.gif)
Comment in
-
Pericytes Preserve Capillary Integrity to Prevent Kidney Hypoxia.J Am Soc Nephrol. 2017 Mar;28(3):717-719. doi: 10.1681/ASN.2016111157. Epub 2016 Dec 15. J Am Soc Nephrol. 2017. PMID: 27979991 Free PMC article. No abstract available.
References
-
- Amdur RL, Chawla LS, Amodeo S, Kimmel PL, Palant CE: Outcomes following diagnosis of acute renal failure in U.S. veterans: focus on acute tubular necrosis. Kidney Int 76: 1089–1097, 2009 - PubMed
-
- Basile DP: Rarefaction of peritubular capillaries following ischemic acute renal failure: a potential factor predisposing to progressive nephropathy. Curr Opin Nephrol Hypertens 13: 1���7, 2004 - PubMed
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources