Transcriptomic Profiling of Hur Expression in the Lung in COPD
Bibliographic record
Abstract
Abstract Introduction: The RNA binding protein (RBP) Human antigen R (HuR) is a ubiquitously expressed member of the embryonic lethal and altered vision like family of protein. It is predominantly a nuclear protein; however, cellular stressors induce its translocation to the cytoplasm to alter the decay and/or translation of mRNAs, which regulate cell proliferation, antioxidant expression and inflammation. Cigarette smoke damages the airway epithelium and fixing this damage requires an elaborate coordination of cellular responses. HuR binds to the 3’ Adenylate-uridylate-rich elements (ARE) of mRNA to determine mRNA fate (Figure 1). Depending on the target and cellular context, HuR can promote mRNA stability and translation, mRNA stability and sequestration or miRNA mediated mRNA degradation. By affecting mRNA translation, storage or decay, HuR regulates up to 15% of the cellular transcriptome. Given its impact, it is important to understand whether HuR expression changes within the lungs of COPD subjects to alter gene expression and proliferative, antioxidant and inflammatory responses in this disease. Methods: Primary human airway epithelial cells (HAECs) were isolated from the lungs of age-matched control subjects and subjects with GOLD C COPD. Healthy and COPD HAECs were grown to 70-80% confluence in 6-well plates and then cell lysate protein and mRNA was collected. Immunoblots for HuR and GAPDH (loading control) were conducted on the cell lysates. Densitometric analysis quantified differences between groups. Quantitative PCR for HuR and b-actin was conducted on cDNA isolated from the mRNA of these HAECs. Single cell sequencing was conducted on cells isolated from paraffin-embedded, formalin fixed lung tissue from smokers with and without COPD (N=2 per group). Results: HuR mRNA expression is decreased in HAECs isolated from COPD subjects (Figure 2A). HuR protein expression is decreased in HAECs isolated from COPD subjects (Figure 2B and 2C). Single cell sequencing of cells isolated from the lungs of age-matched healthy and COPD subjects demonstrated differential expression of HuR expression in COPD (Figure 3). Consistent with our in vitro studies, we found decreased HuR expression in ciliated airway epithelial cells and Club cells. Conclusions: These studies determined that HuR expression was decreased within the airway epithelium in COPD. Conceivably, HuR depletion could enhance smoke-mediated damage by hindering airway epithelial repair and antioxidant responses. Future studies will evaluate the impact of HuR depletion in COPD by smoke-exposing airway specific HuR knockout mice to chronic cigarette smoke exposure (Figure 4).
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 | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".