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Structural analysis of how podocytes detach from the glomerular basement membrane under hypertrophic stress.

Kriz W, Hähnel B, Hosser H, Rösener S, Waldherr R - Front Endocrinol (Lausanne) (2014)

Bottom Line: We studied this process in the rat after growth stimulation with FGF-2.This occurred in microdomains within the same podocyte; thus, features of detachment and of reinforced attachment may simultaneously be found in the same podocyte. (1) Initially, hypertrophied podocytes underwent cell body attenuation and formed large pseudocysts, i.e., expansions of the subpodocyte space. (2) Podocytes entered the process of FPE starting with the retraction of foot processes (FPs) and the replacement of the slit diaphragm by occluding junctions, thereby sealing the filtration slits.Successful completion of this process led to broad attachments of podocyte cell bodies to the GBM. (3) Failure of sealing the slits led to gaps of varying width between retracting FPs facilitating the outflow of the filtrate from the GBM. (4) Since those gaps are frequently overarched by broadened primary processes, the drainage of the filtrate into the Bowman's space may be hindered leading to the formation of small pseudocysts associated with bare areas of GBM. (5) The merging of pseudocysts created a system of communicating chambers through which the filtrate has to pass to reach Bowman's space.

View Article: PubMed Central - PubMed

Affiliation: Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg , Mannheim , Germany ; Institute of Neuroanatomy, Medical Faculty Mannheim, University of Heidelberg , Mannheim , Germany.

ABSTRACT
Podocytes are lost by detachment from the GBM as viable cells; details are largely unknown. We studied this process in the rat after growth stimulation with FGF-2. Endothelial and mesangial cells responded by hyperplasia, podocytes underwent hypertrophy, but, in the long run, developed various changes that could either be interpreted showing progressing stages in detachment from the GBM or stages leading to a tighter attachment by foot process effacement (FPE). This occurred in microdomains within the same podocyte; thus, features of detachment and of reinforced attachment may simultaneously be found in the same podocyte. (1) Initially, hypertrophied podocytes underwent cell body attenuation and formed large pseudocysts, i.e., expansions of the subpodocyte space. (2) Podocytes entered the process of FPE starting with the retraction of foot processes (FPs) and the replacement of the slit diaphragm by occluding junctions, thereby sealing the filtration slits. Successful completion of this process led to broad attachments of podocyte cell bodies to the GBM. (3) Failure of sealing the slits led to gaps of varying width between retracting FPs facilitating the outflow of the filtrate from the GBM. (4) Since those gaps are frequently overarched by broadened primary processes, the drainage of the filtrate into the Bowman's space may be hindered leading to the formation of small pseudocysts associated with bare areas of GBM. (5) The merging of pseudocysts created a system of communicating chambers through which the filtrate has to pass to reach Bowman's space. Multiple flow resistances in series likely generated an expansile force on podocytes contributing to detachment. (6) Such a situation appears to proceed to complete disconnection generally of a group of podocytes owing to the junctional connections between them. (7) Since such groups of detaching podocytes generally make contact to parietal cells, they start the formation of tuft adhesions to Bowman's capsule.

No MeSH data available.


Related in: MedlinePlus

Clustering of podocytes in Bowman’s space is associated with shrinkage of the mesangio-capillary area. The GBM is highlighted in yellow, capillary lumens in green, the PBM and cell nuclei of parietal cells in brown, podocyte cell nuclei in violet. Glomerular profile with a tuft that is broadly connected to Bowman’s capsule by a large cellular crescent that surrounds the tuft from three sides. The mesangio-capillary area (delimited by the GBM) is small compared to the area occupied by podocytes. Note that podocyte cell bodies (visualized by their cell nuclei) have almost completely disappeared from central tuft areas being all contained within the crescent. Most of the podocytes have retained pseudocysts. The cluster of podocytes on top of the tuft does not show any contacts to the tuft nor to the PBM, whereas the major part of the crescent displays extensive contacts to the GBM as well as to Bowman’s capsule. Nuclei of cells, which by no plausible criterion can be assigned as podocytes or parietal cells are uncolored. Note that the GBM is heavily wrinkled at several sites and the mesangial area appears to be collapsed with disappearance of capillaries at several loci (asterisks). Male rat, growth stimulation with FGF-2 for 13 weeks. TEM. Bar: 10 μm.
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Figure 5: Clustering of podocytes in Bowman’s space is associated with shrinkage of the mesangio-capillary area. The GBM is highlighted in yellow, capillary lumens in green, the PBM and cell nuclei of parietal cells in brown, podocyte cell nuclei in violet. Glomerular profile with a tuft that is broadly connected to Bowman’s capsule by a large cellular crescent that surrounds the tuft from three sides. The mesangio-capillary area (delimited by the GBM) is small compared to the area occupied by podocytes. Note that podocyte cell bodies (visualized by their cell nuclei) have almost completely disappeared from central tuft areas being all contained within the crescent. Most of the podocytes have retained pseudocysts. The cluster of podocytes on top of the tuft does not show any contacts to the tuft nor to the PBM, whereas the major part of the crescent displays extensive contacts to the GBM as well as to Bowman’s capsule. Nuclei of cells, which by no plausible criterion can be assigned as podocytes or parietal cells are uncolored. Note that the GBM is heavily wrinkled at several sites and the mesangial area appears to be collapsed with disappearance of capillaries at several loci (asterisks). Male rat, growth stimulation with FGF-2 for 13 weeks. TEM. Bar: 10 μm.

Mentions: Initially, those clusters of podocytes are connected to the GBM by the innermost cells (Figure 4A). In later stages, they made contact via the outermost cells with the parietal epithelium (Figures 4B,C and 5), thereby forming multicellular “bridges” between the GBM and the parietal epithelium. During this process, podocytes change in shape. Apparently by shedding of the pseudocysts, i.e., of their thin walls, the detached podocytes turned into groups of rounded cells without any matrix in between (Figures 4 and 5). Mitotic figures were never encountered in these cells.


Structural analysis of how podocytes detach from the glomerular basement membrane under hypertrophic stress.

Kriz W, Hähnel B, Hosser H, Rösener S, Waldherr R - Front Endocrinol (Lausanne) (2014)

Clustering of podocytes in Bowman’s space is associated with shrinkage of the mesangio-capillary area. The GBM is highlighted in yellow, capillary lumens in green, the PBM and cell nuclei of parietal cells in brown, podocyte cell nuclei in violet. Glomerular profile with a tuft that is broadly connected to Bowman’s capsule by a large cellular crescent that surrounds the tuft from three sides. The mesangio-capillary area (delimited by the GBM) is small compared to the area occupied by podocytes. Note that podocyte cell bodies (visualized by their cell nuclei) have almost completely disappeared from central tuft areas being all contained within the crescent. Most of the podocytes have retained pseudocysts. The cluster of podocytes on top of the tuft does not show any contacts to the tuft nor to the PBM, whereas the major part of the crescent displays extensive contacts to the GBM as well as to Bowman’s capsule. Nuclei of cells, which by no plausible criterion can be assigned as podocytes or parietal cells are uncolored. Note that the GBM is heavily wrinkled at several sites and the mesangial area appears to be collapsed with disappearance of capillaries at several loci (asterisks). Male rat, growth stimulation with FGF-2 for 13 weeks. TEM. Bar: 10 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4264519&req=5

Figure 5: Clustering of podocytes in Bowman’s space is associated with shrinkage of the mesangio-capillary area. The GBM is highlighted in yellow, capillary lumens in green, the PBM and cell nuclei of parietal cells in brown, podocyte cell nuclei in violet. Glomerular profile with a tuft that is broadly connected to Bowman’s capsule by a large cellular crescent that surrounds the tuft from three sides. The mesangio-capillary area (delimited by the GBM) is small compared to the area occupied by podocytes. Note that podocyte cell bodies (visualized by their cell nuclei) have almost completely disappeared from central tuft areas being all contained within the crescent. Most of the podocytes have retained pseudocysts. The cluster of podocytes on top of the tuft does not show any contacts to the tuft nor to the PBM, whereas the major part of the crescent displays extensive contacts to the GBM as well as to Bowman’s capsule. Nuclei of cells, which by no plausible criterion can be assigned as podocytes or parietal cells are uncolored. Note that the GBM is heavily wrinkled at several sites and the mesangial area appears to be collapsed with disappearance of capillaries at several loci (asterisks). Male rat, growth stimulation with FGF-2 for 13 weeks. TEM. Bar: 10 μm.
Mentions: Initially, those clusters of podocytes are connected to the GBM by the innermost cells (Figure 4A). In later stages, they made contact via the outermost cells with the parietal epithelium (Figures 4B,C and 5), thereby forming multicellular “bridges” between the GBM and the parietal epithelium. During this process, podocytes change in shape. Apparently by shedding of the pseudocysts, i.e., of their thin walls, the detached podocytes turned into groups of rounded cells without any matrix in between (Figures 4 and 5). Mitotic figures were never encountered in these cells.

Bottom Line: We studied this process in the rat after growth stimulation with FGF-2.This occurred in microdomains within the same podocyte; thus, features of detachment and of reinforced attachment may simultaneously be found in the same podocyte. (1) Initially, hypertrophied podocytes underwent cell body attenuation and formed large pseudocysts, i.e., expansions of the subpodocyte space. (2) Podocytes entered the process of FPE starting with the retraction of foot processes (FPs) and the replacement of the slit diaphragm by occluding junctions, thereby sealing the filtration slits.Successful completion of this process led to broad attachments of podocyte cell bodies to the GBM. (3) Failure of sealing the slits led to gaps of varying width between retracting FPs facilitating the outflow of the filtrate from the GBM. (4) Since those gaps are frequently overarched by broadened primary processes, the drainage of the filtrate into the Bowman's space may be hindered leading to the formation of small pseudocysts associated with bare areas of GBM. (5) The merging of pseudocysts created a system of communicating chambers through which the filtrate has to pass to reach Bowman's space.

View Article: PubMed Central - PubMed

Affiliation: Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg , Mannheim , Germany ; Institute of Neuroanatomy, Medical Faculty Mannheim, University of Heidelberg , Mannheim , Germany.

ABSTRACT
Podocytes are lost by detachment from the GBM as viable cells; details are largely unknown. We studied this process in the rat after growth stimulation with FGF-2. Endothelial and mesangial cells responded by hyperplasia, podocytes underwent hypertrophy, but, in the long run, developed various changes that could either be interpreted showing progressing stages in detachment from the GBM or stages leading to a tighter attachment by foot process effacement (FPE). This occurred in microdomains within the same podocyte; thus, features of detachment and of reinforced attachment may simultaneously be found in the same podocyte. (1) Initially, hypertrophied podocytes underwent cell body attenuation and formed large pseudocysts, i.e., expansions of the subpodocyte space. (2) Podocytes entered the process of FPE starting with the retraction of foot processes (FPs) and the replacement of the slit diaphragm by occluding junctions, thereby sealing the filtration slits. Successful completion of this process led to broad attachments of podocyte cell bodies to the GBM. (3) Failure of sealing the slits led to gaps of varying width between retracting FPs facilitating the outflow of the filtrate from the GBM. (4) Since those gaps are frequently overarched by broadened primary processes, the drainage of the filtrate into the Bowman's space may be hindered leading to the formation of small pseudocysts associated with bare areas of GBM. (5) The merging of pseudocysts created a system of communicating chambers through which the filtrate has to pass to reach Bowman's space. Multiple flow resistances in series likely generated an expansile force on podocytes contributing to detachment. (6) Such a situation appears to proceed to complete disconnection generally of a group of podocytes owing to the junctional connections between them. (7) Since such groups of detaching podocytes generally make contact to parietal cells, they start the formation of tuft adhesions to Bowman's capsule.

No MeSH data available.


Related in: MedlinePlus