Laboratory Investigation

Kidney International (1981) 20, 549–562; doi:10.1038/ki.1981.176

Investigations of cytoplasmic contractile and cytoskeletal elements in the kidney glomerulus

Peter M Andrews1

1Georgetown University, Department of Anatomy, School of Medicine, Washington, District of Columbia

Correspondence: Dr P M Andrews, Georgetown University, Department of Anatomy, School of Medicine, Washington, District of Columbia 20007, USA

Received 25 June 1980; Revised 13 February 1981.

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Abstract

Investigations of cytosplasmic contractile and cytoskeletal elements in the kidney glomerulus. Electron microscopy and in vitro techniques were used to evaluate the morphologic responses of glomerular podocytes and glomerular endothelial cells to compounds that affect either cytoplasmic contractile elements or cytoplasmic microtubules. In response to in vitro incubation in the presence of cytochalasin D or B (compounds that inhibit contraction of actin-like microfilaments), podocyte foot processes change in shape from short processes with broad bases to taller processes with narrow bases. Coincident with these shape changes, there is an increase in the number of fully patent filtration slit spaces between adjacent foot processes. In view of these observations, it is proposed that glomerular podocytes have the potential for monitoring the filtration slit area available for solute efflux across the glomerular wall by modifying the shapes of their foot processes (that is, expanding and contracting the bases of these structures). As in vitro incubation continues for 1 to 2 days, the cytochalasins inhibit the shape changes of glomerular podocytes that normally occur during 2 days of in vitro incubation—the loss of foot processes, filtration slits, endothelial pores, and thickening of the endothelium. The cytochalasins also inhibit the loss of foot processes and filtration slits that otherwise occur in response to enzymatic removal of glomerular-free surface sialic acid. The in vitro depolymerization of glomerular microtubules by any of a variety of drugs (for example, vinblastine sulfate, colchicine) results in the rounding up of podocyte cell bodies, the thinning of podocyte major processes, and a partial collapsing of the glomerular endothelial walls. These latter observations suggest that microtubules play an important cytoskeletal role in maintaining the structural integrity of these cells.

Etude des éléments contractiles et cytosquelettiques dans le glomérule rénal. La microscopie électronique et les techniques in vitro ont été utilisées pour évaluer le réponse morphologique des podocytes glomérulaires et des cellules endothéliales glomérulaires à des composés qui affectent les éléments contractiles du cytoplasme ou les microtubules. En réponse à l'incubation in vitro en présence de cytochalasine D ou B (des composés qui inhibent la contraction des microfilaments semblables à l'actine), les processus pédiculés changent de forme et passent de celle des processus courts à bases larges à des processus longs à bases étroites. En même temps que les modifications de forme il y a une augmentation dans le nombre des fentes de filtration totalement perméables entre des processus adjacents. En fonction de ces observations il est proposé que les podocytes glomérulaires ont la capacité de moduler la surface de fentes de filtration disponible pour l'efflux à travers la paroi glomérulaire en modifiant la forme des processus pédiculés (c'est-à-dire en étendant ou en contractant la base de ces structures). Quand l'incubation est poursuivie pendant un ou deux jours, les cytochalasines inhibent les modifications de forme des podocytes glomérulaires, la perte des processus pédiculés, des fentes de filtration, des pores endothéliaux et l'épaississement de l'endothélium qui prennent place normalement dans les deux jours d'incubation in vitro. Les cytochalasines inhibent aussi la perte des processus et des fentes de filtration qui sont observés en réponse à la soustraction enzymatique de l'acide sialique libre à la surface des glomérules. La dépolymérisation in vitro des microtubules glomérulaires par une série de drogues (sulfate de vinblastine, colchicine) a pour résultat la transformation des corps cellulaires des podocytes, l'amincissement des processus principaux des podocytes et l'effondrement partiel des parois endothéliales des glomérules. Ces dernières observations suggèrent que les microtubules jouent un rôle important de cytosquelette en maintenant l'intégrité structurale des cellules.

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