Bag3 as a Potential Mechanoprotector in Podocytes
Bibliographic record
Abstract
Background: Podocyte loss is a hallmark of glomerular diseases leading to glomerulosclerosis and progresssion of kidney disease. Sitting on the outside of the glomerular tuft podocytes have to withstand extensive mechanical stress due to perfusion and filtration. Hyperfiltration und hyperperfusion e.g. in disease states cause podocyte detachment when overwhelming their mechonoprotective capacity, which start a vicious cycle of mounting strain on the remaining podocytes. Bag3 is an important mechanoprotector in many mechanical strained tissues and by inducing chaperoneassisted autophagy (CASA) maintains the proteostasis of e.g. Filamin and Synaptopodin - indispensable for podocyte biology. Additionally Bag3 insufficiency renders susceptibility to diabetic nephropathy in a mouse model. These findings point toward Bag3 as a candidate for mechanical stress protection in podocytes. Methods: Using immunofluorescence, super-resolution-microscopy and massspectrometry we examined glomeruli and podocytes for Bag3/CASA expression and characterized the CASA-complex composition in podocytes by immunoprecipitation. The influence of mechanical clues was examined by stiff matrices and cyclic stretch. The role of Bag3 in vivo is being evaluated in different mouse lines (Bag3.P209L mutation, a conditional knockout, fusion-protein). Results: In the glomerulus the Bag3 and the entire CASA-complex is enriched in podocytes in mass-spectrometry. Bag3 staining localizes to the slit diaphragm protein nephrin in superresolution microscopy. Importantly the co-chaperone Bag3 shows interaction with essential actin-cytoskeleton regulators like RhoA, Arpc2 and Dynamin2 in co-immunoprecipitation. The expression of Bag3 and the CASA-complex in podocytes is regulated by mechanical clues. Knockdown of the Bag3 homologue starvin in drosophila nephrocytes displays a mild filtration disturbance. The dominant-negative Bag3.P209L mutation causes a mild proteinuria in a whole-body overexpression mouse line. Conclusions: The data further emphasize the role of Bag3 and chaperone-assistedselective-autophagy in podocyte mechanoprotection and maintenance of podocyte cytoskeleton architecture. Currently undergoing characterization of podocyte specific Bag3 mouse lines and the use of disease models will further help to understand the role of Bag3 at the kidney filtration barrier. Funding: Government Support - Non-U.S.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".