Normal human macula densa morphology and cell turnover: A histological, ultrastructural, and immunohistochemical investigation

Abstract

The aim was to analyze the morphology of normal human macula densa (MD), evaluate the cells that may be responsible for its turnover, and collect quantitative data. Of four samples of normal human renal tissue, two were embedded in resin to measure the longitudinal extension and examine the ultrastructure of the MD, the other two were embedded in paraffin to study apoptosis and cell proliferation. The MD is composed of a monolayer tissue about 40 μm long, which includes 35-40 cells arranged in overlapping rows. Ultrastructurally, MD cells show two polarized portions: an apical end, with sensory features, and a basolateral aspect, with paracrine function. MD cells are connected apically by tight junctions, with/without adherens junctions, which form a barrier between the distal tubule lumen and the interstitium. Cells in degeneration, often associated with macrophages, and undifferentiated cells were found in the MD and adjacent distal tubule. A filamentous mat previously described in proximal tubule scattered tubular cells (STCs) was detected in the basal cytoplasm in undifferentiated cells. The tissue was consistently negative for the proliferation marker Ki67 and for the apoptotic markers caspase-3 and caspase-9. This work confirms our earlier morphological findings and provides new data: (a) MD cells display both apical adherens and tight junctions, the latter forming a tubulo-mesangial barrier; (b) the MD is a monolayer made up of about 40 cells arranged in rows; (c) the simultaneous presence of degenerating (8-13%) and undifferentiated (4-13%) cells reminiscent of STCs suggests a non-negligible cell turnover.

Physiological activation of the nephron central command drives endogenous kidney tissue regeneration

“…Future work is needed to dissect their roles in MD cells. The known structural and neuron-like functional heterogeneity between individual MD cells (7,11,35) was reflected also in their regenerative gene profile established by single-cell transcriptome analysis (Fig. 2C).…”

Identification of multinucleated cells in human kidney cortex: A way for tissue repairing?

“…One‐hundred and forty‐nine podocytes were analysed and six were multinucleated (4%; 95%CI: 1.5%–8.6%) (Table 2). We suggest that these multinucleated cells can be considered as resident parenchymal cells that together with scattered tubular cells (Angelotti et al, 2012; Hansson et al, 2014; Kang et al, 2016; Lazzeri et al, 2018, 2019; Lindgren et al, 2011; Lorenzi et al, 2020; Rinkevich et al, 2014; Smeets et al, 2013) have the capacity to maintain renal tissue homeostasis. The presence of multinucleated cells has been previously demonstrated in the liver (Figure 3b) (Kudryavtsev et al, 1993; Wang et al, 2017) and polyploidy was demonstrated in accordance to the different grades of hepatocyte maturity, i.e.…”

Neuronal nitric oxyde synthase positive neurons in human indusium griseum

“…The Avidin–Biotin-Complex with peroxidase method (ABC; Vector Laboratories) was performed for 1 h at RT, and 3-3′ diaminobenzidine hydrochloride (DAB; Sigma-Aldrich, St Louis, MO, USA) was used as chromogen. Normal human renal macula densa tissue was used as positive control for nNOS (Lorenzi et al 2020 ). Immunostained sections were inspected with a motorized Leica DM6000 microscope (Leica Microsystems, Wetzlar, Germany), using different magnifications (10×, 25× and 40×).…”