Specific Role of Adiponectin in Pulmonary Artery Smooth Muscle Cells Proliferation and Inflammatory Cytokines Production during Rat Lung Development
Bibliographic record
Abstract
Adiponectin (APN), an abundant circulating plasma protein mostly generated from adipose tissue, is implicated in lung vascular, oxidative and anti‐inflammatory protection. Circulating APN levels are low in premature and small for gestational age neonates, who are at the greatest risk for developing lung oxidative and inflammatory injury leading to bronchopulmonary (BPD) and pulmonary artery hypertension (PAH). We previously characterized the expression pattern of APN and its receptors (Adipor1 and Adipor2) during lung development in the newborn rat and localized APN and Adipor1 and Adipor2 protein expression in pulmonary artery smooth muscle cells (PASMC). Here we describe the effect of recombinant APN (rAPN) on PASMC proliferation and pro‐ and anti‐inflammatory cytokine production in PASMC during early lung development. METHODS Postnatal day (PND) 4 and 7 PASMC were treated with recombinant APN (rAPN) (2 and 5 μg/ml), in the presence of water‐soluble tetrazolium salt 8 (WST8). The formation of formazan in viable cells was detected spectrophotometrically and used as an indicator of cell proliferation. The effect of rAPN on lipopolysaccharide (LPS) (3 μg/ml) ‐ induced protein expression of IL6, TNFα, and IL10 was also examined. Western blotting technique were used to measure cytokine protein expression. RESULTS rAPN decreased the proliferation of PASMC from both age groups, p<0.05 vs only culture medium control cells. rAPN (2μg/ml): 1) decreased IL6 protein levels in PND 4 PASMC at baseline and in presence of LPS with no effect on IL‐6 expression in PASMC from PND 7 animals, 2) decreased TNFα protein levels in PND 4 and PND 7 PASMC in response to LPS and at baseline only in PND 4 PASMC, and 3) increased the anti‐inflammatory cytokine IL10 protein levels from PASMC at baseline in PND4 and in response to LPS in PND 7 (p<0.05 vs control) CONCLUSIONS For the first time, we show that rAPN inhibits PASMC proliferation and pro‐inflammatory cytokine production in PASMC during early postnatal lung development. Overall rAPN decreased pro‐inflammatory and increased anti‐inflammatory cytokine production in these cells at PND 4 and 7. These novel findings are relevant to the premature infant at high risk for developing BPD and associated PAH. We speculate that increasing lung APN levels could potentially decrease lung injury and vascular remodeling from inflammatory stimuli and reduce the development of BPD. The role of rAPN delivered to the lung, in an in vivo model of LPS‐induced lung injury in newborn rats is currently being investigated Support or Funding Information Women's Auxilary of The Hospital for Sick Children This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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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 | 0.001 | 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) | 0.000 | 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".