Neuronal proteins are novel components of podocyte major processes and their expression in glomerular crescents supports their role in crescent formation

Abstract

The podocyte has a central role in the glomerular filtration barrier typified by a sophisticated morphology of highly organized primary (major) and secondary (foot) processes. The molecular makeup of foot processes is well characterized, but that of major processes is poorly known. Previously, we profiled the glomerular transcriptome through large-scale sequencing and microarray profiling. Unexpectedly, the survey found expression of three neuronal proteins (Huntingtin interacting protein 1 (Hip1), neurofascin (Nfasc), and olfactomedin-like 2a (Olfml2a)), all enriched in the glomerulus. These proteins were expressed exclusively by podocytes, wherein they localized to major processes as verified by RT-PCR, western blotting, immunofluorescence, and immunoelectron microscopy. During podocyte development, these proteins colocalized with vimentin, confirming their association with major processes. Using immunohistochemistry, we found coexpression of Hip1 and Olfml2a along with the recognized podocyte markers synaptopodin and Pdlim2 in glomerular crescents of human kidneys, indicating the presence of podocytes in these lesions. Thus, three neuronal proteins are highly expressed in podocyte major process. Using these new markers we found that podocytes contribute to the formation of glomerular crescents.

APOL1 Kidney Disease Risk Variants: An Evolving Landscape

“…Interestingly, the podocyte, the central target in several APOL1 nephropathies, shares characteristics with neurons. Certain proteins that are expressed by podocytes and implicated in glomerulopathies, such as podocin, nephrin, podocalxyin, and synaptopodin, are also important neuronal markers, indicating some degree of transcriptome similarity [80,81]. Furthermore, podocyte foot processes display some similarities to neuronal dendrites [82].…”

Aspectos histopatológicos das lesões renais em gatos experimentalmente infectados pelo vírus da imunodeficiência felina

“…Entretanto, ainda há controvérsias a respeito da origem das células hiperplásicas no interior dos glomérulos (Bruggeman & Nelson 2009). Alguns estudos, nos quais marcadores celulares foram utilizados, sugerem que as cé-lulas presentes nas pseudocrescentes na HIVAN e em outras glomerulopatias colapsantes se originem das células epiteliais parietais e não dos podócitos (Nagata et al 1998, Dijkman et al 2006, ao passo que os podócitos também podem contribuir, de certa maneira, para a formação das crescentes glomerulares (Thorner et al 2008, Sistani et al 2012. Os resultados conflitantes caracterizados pela detecção de alguns marcadores específicos de podócitos nas crescentes glomerulares e não detecção de outros poderia ser explicado pela diferenciação dos podócitos e perda de alguns marcadores específicos com a progressão da doença (Sistani et al 2012).…”

Vitamin D (25 ( OH) D ) in patients with chronic kidney disease stages 2-5

“…Chronic kidney disease was defined according to the 2013 KDIGO guidelines 13. It was classified on stages according to the estimated GFR by the MDRD formula.…”