Transforming growth factor beta 1 (TGF-β1), a cytokine whose levels are elevated in the airways of patients with asthma, perpetuates airway inflammation and modulates airway structural cell remodeling. However, the role of TGF-β1 in excessive airway narrowing in asthma, or airway hyperresponsiveness (AHR), remains unclear. In this study, we set out to investigate the direct effects of TGF-β1 on human airway smooth muscle (HASM) cell shortening and hyperresponsiveness. The dynamics of AHR and single-cell excitation-contraction (E-C) coupling were measured in human precision-cut lung slices (hPCLS) and in isolated HASM cells using supravital microscopy and magnetic twisting cytometry (MTC), respectively. In hPCLS, overnight treatment with TGF-β1 significantly augmented basal and carbachol-induced bronchoconstriction. In isolated HASM cells, TGF-β1 increased basal and methacholine-induced cytoskeletal stiffness in a dose- and time-dependent manner. TGF-β1-induced single-cell contraction was corroborated by concomitant increases in myosin light chain (MLC) and myosin phosphatase target subunit 1 (MYPT1) phosphorylation levels, which were attenuated by siRNA-mediated knockdown of Smad3 and pharmacological inhibition of Rho kinase. Strikingly, these physiologic effects of TGF-β1 occurred through a RhoA-independent mechanism with little effect on HASM cell [Ca2+]i levels. Together, our data suggest that TGF-β1 enhances HASM E-C coupling pathways to induce HASM cell shortening and hyperresponsiveness. These findings reveal a potential link between airway injury-repair responses and bronchial hyperreactivity in asthma, and define TGF-β1 signaling as a potential target to reduce AHR in asthma.
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 May 2018.
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#9,494,398
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#1,177
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#124,606
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Outputs of similar age from American Journal of Respiratory Cell and Molecular Biology
#17
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Altmetric has tracked 30,092,955 research outputs across all sources so far. This one has received more attention than most of these and is in the 68th percentile.
So far Altmetric has tracked 3,923 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.4. This one has gotten more attention than average, scoring higher than 69% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 340,303 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 62% of its contemporaries.
We're also able to compare this research output to 60 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 70% of its contemporaries.
