Projects

Role of pericyte angiotensin receptor signaling in kidney disease

Pericytes are an important vascular cell type in the kidney. In addition to supporting endothelial cells in capillaries, they also have specialized functions in the glomerulus, where they are referred to as mesangial cells.

Recent single-cell RNAseq datasets have revealed that pericytes express abundant amounts of the type 1a angiotensin receptor (Figure 1). We hypothesize that this means that pericytes are playing a major role in kidney disease.

Our lab is exploring the role of pericyte angiotensin receptor signaling in kidney disease by conditionally knocking out the angiotensin receptor from pericytes with the Pdgfrb-creERT2 (Figure 2). We are looking at how this affects kidney phenotypes in both Angiotensin II induced hypertension as well as diabetic kidney disease.

This project is supported by the NIDDK (1K01DK121737) AHA (20CDA35320169)

Figure 1 mesangial cell population
Figure 1. Pericytes Express Angiotensin Receptor in the Kidney. A) T-SNE plot of single-cell RNAseq dataset obtained from mouse tissue with different cell populations labeled (Wu et al26). B) Expression of the AT1aR (Gene Name Agtr1a) overlayed onto the t-SNE plot from A. C) Expression of the Pdgfrb overlayed onto the t-SNE plot from A. D) Dot Plot of AT1aR expression in different kidney cell populations. Purple arrow points towards the pericyte population termed mesangial cells.
Figure 2 glomerulus histology GFP vs CD31
Figure 2. Pdgfrβ-CreERT2 Cre Targets Pericytes in the Kidney. Mice were injected with CD31 conjugated to A594 to label the vasculature and crossed to a GFP reporter mouse. Cspg4-creERT2 activity in the Cortex (A) and Medulla (B). Imaging of Pdgfrβ-CreERT2 in the Cortex (C) (arrowhead points to mesangial cells (glomerulus), and arrows point to interstitial pericytes) in medulla (D). Tile Scan of kidney showing extensive Cre activity in pericytes (E).