Pathogenesis of Pulmonary Fibrosis - The Role of Extracellular Heat Shock Protein-90 (HSP90) in Myofibroblast Differentiation and Persistence
Bibliographic record
Abstract
Idiopathic pulmonary fibrosis (IPF) is characterized by extensive extracellular matrix (ECM) deposition. ECM from fibrotic lungs, mainly produced by myofibroblasts, is stiffer than non-fibrotic ECM increasing mechanical stress. The ECM is a major storage compartment for extracellular proteins which affect pulmonary cells’ behavior. HSP90 belongs to the heat shock protein (HSP) family that are involved in various pathologic processes. HSP90 is secreted by cells subjected to stress conditions and promotes matrix metalloproteinase activation, integrin upregulation and epithelial-to-mesenchymal transition; processes involved in fibrogenesis. We hypothesize that eHSP90’s secretion is enhanced in fibrotic conditions and that eHSP90 contributes to the differentiation and persistence of lung myofibroblasts. HSP90 serum level was assessed in IPF patients by ELISA. eHSP90’s release by mechanical stretch was assessed ex vivo in rat fibrotic lung slices. In vitro experiments were performed using recombinant HSP90 and blocking antibodies. We demonstrated that circulating HSP90 is enhanced in IPF patients’ serum and is correlated with IPF severity. HSP90’s secretion was enhanced after mechanical stretch of fibrotic lungs ex vivo and was upregulated in BAL of fibrotic mice in vivo. Recombinant HSP90 induced myofibroblast differentiation indicated by an increase in α-SMA expression, MMP activation and ECM production. We identified that eHSP90 signaled through the membrane receptor LRP-1. HSP90 and LRP-1 inhibition limited myofibroblasts differentiation.
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) | 0.001 | 0.000 |
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".