Glial fibrillary acidic protein‐positive cells of the kidney are capable of raising a protective biochemical barrier similar to astrocytes: Expression of metallothionein in podocytes

Abstract

Blood-tissue exchange and homeostasis within the organs depend on various interactions between endothelial and perivascular cells (Buniatian, 2001). Podocytes possess anatomical and cellular features intermediate between those of astrocytes and hepatic stellate cells (HSCs). Podocytes, like HSCs, are associated with fenestrated capillaries and, similar to astrocytes, interact with the capillaries via the basement membrane and participate in permeability-limiting ultrafiltration. The fact that podocytes come in direct contact with xenobiotics prompted us to investigate whether they express metallothionein (MT), an anticytotoxic system characteristic of astrocytes. In comparative studies, cryosections of 1-and 3-month-old rat kidney and adult rat brain, as well as podocytes and astrocytes from early and prolonged primary cultures of glomerular explants and newborn rat brain, respectively, were investigated. The cells were double-labeled with antiserum against glial fibrillary acidic protein (GFAP) and monoclonal antibody (MAb) against the lysine-containing epitope of Cd/Zn-MT-I (MAb MT) or MAb against alpha-actin. In kidney sections, MT immunoreactivity was detected in GFAP-positive glomerular cells and in interstitial fibroblasts. The pattern of staining for MT and GFAP in glomerular cells was similar to that of astrocytes in vivo. In glomerular cell cultures, MT was expressed in cobblestone-like podocytes which contained Wilms' tumor protein and lacked desmin. MT was upregulated at later culture periods, during which podocytes acquired features typical of undifferentiated astrocytes. This study hints at the existence of common regulatory mechanisms of blood-tissue interactions by neural and non-neural perivascular cells. These mechanisms appear to be used in an organ-specific manner.

Megacolon in Chagas disease: a study of inflammatory cells, enteric nerves, and glial cells

“…In Chagas disease, it was interesting to observe that, despite the overall loss of enteric glial cells, the patients presented increasing percentages of the GFAP-IR population. Being a constituent of the intermediate filaments, one of the functions of GFAP is possibly to increase the cohesion between the glial cells [25]. Considering these observations, it is tempting to speculate that the increased expression of GFAP-IR glial cells in chagasic patients creates a barrier of protection for the neuronal cell bodies and represents thus an attempt to protect ENS neurons against inherent harmful factors of inflammatory processes or against parasite infection.…”

Glial fibrillary acidic protein is a body fluid biomarker for glial pathology in human disease

“…The pattern of non astrocytic GFAP expression at the air-tissue interface may provide functional insight (Danielyan et al, 2007). The authors speculate on a possible protective role as part of an immune-barrier (Buniatian et al, 2002;Danielyan et al, 2007;Hainfellner et al, 2001). These results will need confirmation using a GFAP-KO model as control.…”

“…Non-astrocytic expression and function of GFAP For an updated database with references of the ever extending list of mutations see http://www.waisman.wisc.edu/alexan der-disease/ or http://www.interfil.org/ is mainly immunocytochemical evidence for GFAP in the lens, non-myelinating Schwann cells, testicular Leydig cells, stellate cells of the liver and pancreas, enteric glia, podocytes, mesangial cells and chondrocytes (Apte et al, 1998;Buniatian et al, 2002). The quantitative contribution of such non-CNS derived protein was found to be negligible for neurological biomarker studies (Petzold et al, 2010).…”

Expression of Neural Stem Cell Marker Nestin in the Kidney of Rats and Humans

“…It should be emphasized that the presence of nestin is not the only marker, which illustrates close similarity of the cytoskeleton in podocytes and nerve cells. Intermediate filaments of podocytes contain glial fibrillary acidic protein [6], which serves as a specific marker of astrocytes [3]. The data attest to either common origin of these cells, or (more likely) to specific functional status of these structural elements of the filtration barrier and blood-brain barrier.…”