<p>Clusterin Deficiency Predisposes C57BL/6j Mice to Cationic Bovine Serum Albumin-Induced Glomerular Inflammation</p>
Bibliographic record
Abstract
BACKGROUND: Membranous nephropathy (MN) is a specific entity of glomerulonephritis, and its glomerular inflammation is characterized by the deposition of immune complexes in the glomerular basement membrane and proteinuria. However, the molecular mechanisms underlying the glomerular inflammation of MN are not fully understood. This study was designed to investigate the role of clusterin (CLU) in the development of MN using a mouse model of cationic bovine serum albumin (cBSA)-induced MN. METHODS: Both wild-type C57BL/6j (WT) and CLU-knockout C57BL/6j (CLU-KO) mice were immunized with cBSA. The kidney function was determined by the levels of serum creatinine (SCr), blood urea nitrogen (BUN) and urinary protein. MN and glomerular deposits of CLU, complement C3 and immunoglobulins (Igs) were determined by histological analyses. Serum proteins were analyzed by the enzyme-linked immunosorbent assay, Western blot and liquid chromatography-mass spectrometry. RESULTS: Here, we showed that after cBSA immunization, SCr and proteinuria were increased in CLU-KO mice but not in WT mice. Similarly, severe glomerular atrophy and mesangial expansion along with C3 deposit were only found in the kidneys of CLU-KO mice but not in WT mice. However, there were no differences of serum IgG and complement 3 levels between CLU-KO and WT mice. In the serum of WT mice, CLU bound to anti-cBSA IgG, complements (eg, C8), proteinase/protease inhibitors and antioxidative proteins to form a complex, and incubation with WT serum reduced the complement-dependent lysis of podocytes in cultures. CONCLUSION: Our data suggest that a CLU deficiency induces cBSA-initiated glomerular inflammation of MN in a disease-resistant strain of mice, suggesting an anti-glomerular inflammatory function of CLU in the resistance to MN development. This function may be at least in part due to the formation of CLU-anti-cBSA Igs complex that prevents glomerular inflammation or injury in the disease-resistant mice.
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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) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 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".