F-actin fiber distribution in glomerular cells: Structural and functional implications

Background. Glomerular distention is associated with cellular mechanical st rain. In addition, glomerular distention/contraction is assumed to influenc e the filtration rate through changes in filtration surface area. A contrac tile cytoskeleton in podocytes and mesangial cells, formed by F-actin-conta ining stress fibers, maintains structural integrity and modulates glomerula r expansion. In this study, the glomerular cell distribution of F-actin and vimentin filaments was studied in normal control and nine-month streptozot ocin-diabetic rats. Results in situ were compared with observations in tiss ue culture. Methods. Microdissected rat glomeruli were perfused to obtain a physiologic al 25% glomerular expansion over the basal value. Fixation was done without change in glomerular volume. Dual fluorescent labeling of F-actin and vime ntin was carried out, and samples were examined by confocal laser scanning microscopy. Results The podocyte cell bodies and their cytoplasmic projections, includi ng the foot processes, contained bundles of vimentin-containing fibers. Exc ept for a thin layer at the base of foot processes, they did not demonstrat e F-actin. White mesangial cells in culture had F-actin as long stress fibe rs resembling tense cables, mesangial cells stretched in situ contained a m aze of short tortuous F-actin fibers organized in bundles that often encirc led vascular spaces. This fibrillar organization was disrupted in diabetic glomeruli. Conclusion. Mesangial cells, but not podocytes, contain a cytoskeleton capa ble of contraction that is disorganized in long-term diabetes. Together wit h previous observations, the distribution of this cytoskeleton suggests tha t mesangial cell contraction may be involved in the redistribution of glome rular capillary blood flow, but not substantially in the modulation of glom erular distention. Disorganization of stress fibers may be a cause of hyper filtration in diabetes.