Department of Physiology & Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV, USA.
J Physiol. 2020 Aug;598(15):3283-3307. doi: 10.1113/JP278888. Epub 2020 Jun 8.
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.
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.
血小板衍生生长因子受体-α（PDGFRα）是一种新型生物标志物，与平滑肌肌球蛋白重链一起存在于小鼠和食蟹猴肾盂-肾盏交界处的起搏细胞（以前称为“非典型”平滑肌细胞）中。存在于小鼠肾盂外膜和尿路上皮层的 PDGFRα 细胞不表达平滑肌肌球蛋白重链（smMHC），但与神经纤维紧密相邻。大多数肾盏中的 c-Kit 细胞为肥大细胞。肥大细胞（CD117/CD45）在肾盂近端和肾盂-肾盏交界处更为丰富，而 c-Kit 间质细胞（CD117/CD45）主要存在于肾盂远端和肾盂输尿管交界处。PDGFRα 细胞与 c-Kit 间质细胞不同。使用表达遗传编码钙传感器的小鼠，整个肾盂中都有一部分 PDGFRα 细胞表达钙激活的氯离子通道，anoctamin-1。在 c-Kit 间质细胞、smMHC PDGFRα 细胞和 smMHC PDGFRα 细胞中观察到自发的钙瞬变。
肾盂的有节奏收缩将尿液从肾脏输送到输尿管。被称为非典型平滑肌细胞（ASMCs）的特化起搏细胞被认为驱动肾盂中的典型平滑肌细胞（TSMCs）的蠕动收缩。与 ASMCs 和 TSMC 紧密相邻的间质细胞（ICs）已被描述，但这些细胞的作用知之甚少。评估了 PDGFRα 在肾盂-肾盏交界处（PKJ）和远端肾盂中的 ICs 的存在和分布。我们发现 PDGFRα ICs 存在于肾盂的外膜层、PKJ 的肌肉层和远端肾盂的外膜层。PDGFRα ICs 与肾盏中的 c-Kit ICs 不同。c-Kit ICs 是小鼠肾盏中 ICs 的一小部分。大多数 c-Kit 细胞为肥大细胞。PKJ 的 PDGFRα 细胞共表达平滑肌肌球蛋白重链（smMHC）和其他几种平滑肌基因转录本，表明这些细胞是 ASMCs，PDGFRα 是 ASMCs 的新型生物标志物。PDGFRα 细胞还表达 Ano1，其编码钙激活的氯离子电导，作为胃肠道 ICs 的主要起搏电导。使用遗传编码钙传感器，在 c-Kit ICs、smMHC PDGFRα 细胞和 smMHC PDGFRα 细胞中观察到自发的钙瞬变。通过内源性 Pdgfra 启动子驱动增强型绿色荧光蛋白的报告株小鼠被证明是一种强大的新工具，可用于分离和表征这些细胞在肾盏中的表型和功能。
