G Protein‐Coupled Receptors in Human Lung Fibroblasts: Novel Therapeutic Approaches for Idiopathic Pulmonary Fibrosis?
Bibliographic record
Abstract
Idiopathic Pulmonary Fibrosis (IPF) is a progressive, often fatal interstitial lung disease and thus in need of new, effective therapies. A feature of IPF is fibroblast‐to‐myofibroblast transition and resultant increased deposition of extracellular matrix (ECM) proteins, which can lead to loss of functional lung tissue. Previous studies have shown that increases in cyclic AMP (cAMP) can decrease the number and function of myofibroblasts. Cellular synthesis of cAMP is mediated by adenylyl cyclase, the activity of which is regulated by G‐protein signaling and G‐protein coupled receptors (GPCRs). We hypothesized that alteration in GPCR expression in lung fibroblasts from IPF patients may identify new therapeutic targets for lung fibrosis. Using RNA‐seq, we have identified and quantified GPCRs of lung fibroblasts isolated from six IPF patients and six controls grown in low passage primary cultures. RNA‐seq analysis revealed the expression of ~120 GPCRs (of ~380 endoGPCRs [regulated by endogenous ligands]). On average ~20 highly expressed GPCR were detected in all samples, with small differences in biological replicates; these may be “housekeeping” GPCRs. We also identified a group of GPCRs with highly variable expression and found that lung fibroblasts from IPF patients selectively expressed a subset of GPCRs. To assess changes in GPCR expression during fibroblast‐to‐myofibroblast transition, we treated fibroblasts with TGFβ1 (10 ng/ml, 48 hrs or 20 ng/ml, 16 hrs). As expected, TGFβ1 treatment increased the expression of pro‐fibrotic markers (e.g., collagens Iα1, Iα2, III; α‐smooth muscle actin; plasminogen activator inhibitor‐1). In addition, TGFβ1 altered (increased or decreased) the expression of numerous GPCRs. TGFβ1 treatment of control fibroblasts did not fully mimic the GPCR expression changes of fibroblasts from IPF patients. We conclude that GPCR expression (GPCRomic) analysis identifies GPCRs that may contribute to the fibrotic state in the lung and thus, may be novel therapeutic targets for lung fibrosis. Support or Funding Information Supported by NIH T32 HL 098062‐04, Bristol Myers Squibb and CIHR 201403MOP‐RS‐323925. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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) | 0.001 | 0.001 |
| 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 | 0.001 | 0.001 |
| 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".