Identification and classification of interstitial cells in the mouse renal pelvis.

Key Points: Platelet-derived growth factor receptor-α (PDGFRα) is a novel biomarker along with smooth myosin heavy chain for the pacemaker cells (previously termed 'atypical' smooth muscle cells) in the murine and cynomolgus monkey pelvis-kidney junction. PDGFRα cells present in adventitial and urothelial layers of murine renal pelvis do not express smooth muscle myosin heavy chain (smMHC) but are in close apposition to nerve fibres. Most c-Kit cells in the renal pelvis are mast cells. Mast cells (CD117 /CD45 ) are more abundant in the proximal renal pelvis and pelvis-kidney junction regions whereas c-Kit interstitial cells (CD117 /CD45 ) are found predominantly in the distal renal pelvis and ureteropelvic junction. PDGFRα cells are distinct from c-Kit interstitial cells. A subset of PDGFRα cells express the Ca -activated Cl channel, anoctamin-1, across the entire renal pelvis. Spontaneous Ca transients were observed in c-Kit interstitial cells, smMHC PDGFRα cells and smMHC PDGFRα cells using mice expressing genetically encoded Ca sensors.

Abstract: Rhythmic contractions of the renal pelvis transport urine from the kidneys into the ureter. Specialized pacemaker cells, termed atypical smooth muscle cells (ASMCs), are thought to drive the peristaltic contractions of typical smooth muscle cells (TSMCs) in the renal pelvis. Interstitial cells (ICs) in close proximity to ASMCs and TSMCs have been described, but the role of these cells is poorly understood. The presence and distributions of platelet-derived growth factor receptor-α (PDGFRα ) ICs in the pelvis-kidney junction (PKJ) and distal renal pelvis were evaluated. We found PDGFRα ICs in the adventitial layers of the pelvis, the muscle layer of the PKJ and the adventitia of the distal pelvis. PDGFRα ICs were distinct from c-Kit ICs in the renal pelvis. c-Kit ICs are a minor population of ICs in murine renal pelvis. The majority of c-Kit cells were mast cells. PDGFRα cells in the PKJ co-expressed smooth muscle myosin heavy chain (smMHC) and several other smooth muscle gene transcripts, indicating these cells are ASMCs, and PDGFRα is a novel biomarker for ASMCs. PDGFRα cells also express Ano1, which encodes a Ca -activated Cl conductance that serves as a primary pacemaker conductance in ICs of the GI tract. Spontaneous Ca transients were observed in c-Kit ICs, smMHC PDGFRα cells and smMHC PDGFRα cells using genetically encoded Ca sensors. A reporter strain of mice with enhanced green fluorescent protein driven by the endogenous promotor for Pdgfra was shown to be a powerful new tool for isolating and characterizing the phenotype and functions of these cells in the renal pelvis.