Human airway smooth muscle cell proliferation from asthmatics is negatively regulated by semaphorin3A
Bibliographic record
Abstract
// Hesam Movassagh 1 , Nazanin Tatari 1 , Lianyu Shan 1 , Latifa Koussih 1,2 , Duaa Alsubait 1 , Mahdi Khattabi 1 , Naresh S. Redhu 1,3 , Michael Roth 4 , Michael Tamm 4 , Jamila Chakir 5 and Abdelilah S. Gounni 1 1 Department of Immunology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada 2 Université de Saint-Boniface, Winnipeg, Manitoba, Canada 3 Division of Gastroenterology, Hepatology and Nutrition, Boston Children’s Hospital, Boston, MA, USA 4 Department of Biomedicine, Pneumology & Pulmonary Cell Research, University Hospital Basel and University of Basel, Basel, Switzerland 5 Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie du Quebec, Universite´ Laval, Quebec City, Canada Correspondence to: Abdelilah S. Gounni, email: // Keywords : airway remodeling, asthma, neuropilin 1, platelet-derived growth factor, semaphorin 3A, Pathology Section Received : June 19, 2016 Accepted : October 06, 2016 Published : October 25, 2016 Abstract Airway smooth muscle (ASM) hyperplasia is a key feature of airway remodeling in development of lung diseases such as asthma. Anomalous proliferation of ASM cells directly contributes to ASM hyperplasia. However, the molecular mechanisms controlling ASM cell proliferation are not completely understood. Semaphorins are versatile regulators of various cellular processes including cell growth and proliferation. The role of semaphorins in ASM cell proliferation has remained to be addressed. Here, we report that semaphorin 3A (Sema3A) receptor, neuropilin 1 (Nrp1), is expressed on human ASM cells (HASMC) isolated from healthy and asthmatic donors and treatment of these cells with exogenous Sema3A inhibits growth factor-induced proliferation. Sema3A inhibitory effect on HASMC proliferation is associated with decreased tyrosine phosphorylation of PDGFR, downregulation of Rac1 activation, STAT3 and GSK-3β phosphorylation. Bronchial sections from severe asthmatics displayed immunoreactivity of Nrp1, suggestive of functional contribution of Sema3A-Nrp1 axis in airway remodeling. Together, our data suggest Sema3A-Nrp1 signaling as a novel regulatory pathway of ASM hyperplasia.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 teacher head, 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".