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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

Sequence of podocyte disconnection from the GBM. The GBM is highlighted in yellow, capillary lumens in green, and spaces considered as pseodocysts connected to bare GBM in yellow-orange. Individual podocytes are highlighted in different shades of violet. (A) Early stage of podocyte detachment from the GBM. A sealing of filtration slits by occluding junctions replacing slit membranes was only partially successful (arrowheads). At many other sites, retraction of FPs has left behind circumscribed areas of bare GBM (arrows) that start to merge (red dots). (B) Advanced stage of podocyte detachment from the GBM. The dome-shaped spaces (asterisks) above bare areas of GBM have enlarged bulging toward the urinary space. Merging of these spaces leads to a communicating system of pseudocysts (arrows). (C) The pseudocysts (asterisks) increase in size by merging and bulging; they are related to large stretches of bare GBM and overarched by broadened and attenuated primary processes. (D) The final detachment of a podocyte is frequently characterized by the merging of innumerous interconnected (red arrows) pseudocysts that start over bare GBM (red dots) and drain into Bowman’s space (not seen in this section). Other portions of this podocyte may closely stick to the GBM with completed FPE (black arrows). Male rats, growth stimulation with FGF-2 for 13 weeks. TEMs. Bars: (A) 1 μm, (B) 2 μm, (C) 1 μm, (D) 2.5 μm.
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Figure 3: Sequence of podocyte disconnection from the GBM. The GBM is highlighted in yellow, capillary lumens in green, and spaces considered as pseodocysts connected to bare GBM in yellow-orange. Individual podocytes are highlighted in different shades of violet. (A) Early stage of podocyte detachment from the GBM. A sealing of filtration slits by occluding junctions replacing slit membranes was only partially successful (arrowheads). At many other sites, retraction of FPs has left behind circumscribed areas of bare GBM (arrows) that start to merge (red dots). (B) Advanced stage of podocyte detachment from the GBM. The dome-shaped spaces (asterisks) above bare areas of GBM have enlarged bulging toward the urinary space. Merging of these spaces leads to a communicating system of pseudocysts (arrows). (C) The pseudocysts (asterisks) increase in size by merging and bulging; they are related to large stretches of bare GBM and overarched by broadened and attenuated primary processes. (D) The final detachment of a podocyte is frequently characterized by the merging of innumerous interconnected (red arrows) pseudocysts that start over bare GBM (red dots) and drain into Bowman’s space (not seen in this section). Other portions of this podocyte may closely stick to the GBM with completed FPE (black arrows). Male rats, growth stimulation with FGF-2 for 13 weeks. TEMs. Bars: (A) 1 μm, (B) 2 μm, (C) 1 μm, (D) 2.5 μm.

Mentions: Neighboring such developments, even at other aspects of the same podocyte, these protective responses may fail, starting the focal detachment of podocytes at seemingly random sites. The complete detachment of an entire podocyte results from the final coalescence of numerous discrete disconnected areas (Figure 3). The smallest and probably first signs of detachment consist of circumscribed bare areas of GBM encountered in between two FPs of the same podocyte, thus the former interposed FP was missing (Figure 3A). This phenomenon frequently occurs in series and may be derived from the retraction of a series of FPs arising from a common larger process. In such cases, the co-ordinated retraction of adjacent FPs after formation of occluding junctions between them (as described above) seems to have failed.


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)

Sequence of podocyte disconnection from the GBM. The GBM is highlighted in yellow, capillary lumens in green, and spaces considered as pseodocysts connected to bare GBM in yellow-orange. Individual podocytes are highlighted in different shades of violet. (A) Early stage of podocyte detachment from the GBM. A sealing of filtration slits by occluding junctions replacing slit membranes was only partially successful (arrowheads). At many other sites, retraction of FPs has left behind circumscribed areas of bare GBM (arrows) that start to merge (red dots). (B) Advanced stage of podocyte detachment from the GBM. The dome-shaped spaces (asterisks) above bare areas of GBM have enlarged bulging toward the urinary space. Merging of these spaces leads to a communicating system of pseudocysts (arrows). (C) The pseudocysts (asterisks) increase in size by merging and bulging; they are related to large stretches of bare GBM and overarched by broadened and attenuated primary processes. (D) The final detachment of a podocyte is frequently characterized by the merging of innumerous interconnected (red arrows) pseudocysts that start over bare GBM (red dots) and drain into Bowman’s space (not seen in this section). Other portions of this podocyte may closely stick to the GBM with completed FPE (black arrows). Male rats, growth stimulation with FGF-2 for 13 weeks. TEMs. Bars: (A) 1 μm, (B) 2 μm, (C) 1 μm, (D) 2.5 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Sequence of podocyte disconnection from the GBM. The GBM is highlighted in yellow, capillary lumens in green, and spaces considered as pseodocysts connected to bare GBM in yellow-orange. Individual podocytes are highlighted in different shades of violet. (A) Early stage of podocyte detachment from the GBM. A sealing of filtration slits by occluding junctions replacing slit membranes was only partially successful (arrowheads). At many other sites, retraction of FPs has left behind circumscribed areas of bare GBM (arrows) that start to merge (red dots). (B) Advanced stage of podocyte detachment from the GBM. The dome-shaped spaces (asterisks) above bare areas of GBM have enlarged bulging toward the urinary space. Merging of these spaces leads to a communicating system of pseudocysts (arrows). (C) The pseudocysts (asterisks) increase in size by merging and bulging; they are related to large stretches of bare GBM and overarched by broadened and attenuated primary processes. (D) The final detachment of a podocyte is frequently characterized by the merging of innumerous interconnected (red arrows) pseudocysts that start over bare GBM (red dots) and drain into Bowman’s space (not seen in this section). Other portions of this podocyte may closely stick to the GBM with completed FPE (black arrows). Male rats, growth stimulation with FGF-2 for 13 weeks. TEMs. Bars: (A) 1 μm, (B) 2 μm, (C) 1 μm, (D) 2.5 μm.
Mentions: Neighboring such developments, even at other aspects of the same podocyte, these protective responses may fail, starting the focal detachment of podocytes at seemingly random sites. The complete detachment of an entire podocyte results from the final coalescence of numerous discrete disconnected areas (Figure 3). The smallest and probably first signs of detachment consist of circumscribed bare areas of GBM encountered in between two FPs of the same podocyte, thus the former interposed FP was missing (Figure 3A). This phenomenon frequently occurs in series and may be derived from the retraction of a series of FPs arising from a common larger process. In such cases, the co-ordinated retraction of adjacent FPs after formation of occluding junctions between them (as described above) seems to have failed.

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