| First Author | McGowan SE | Year | 2020 |
| Journal | Am J Respir Cell Mol Biol | Volume | 62 |
| Issue | 4 | Pages | 454-465 |
| PubMed ID | 31913651 | Mgi Jnum | J:313260 |
| Mgi Id | MGI:6690791 | Doi | 10.1165/rcmb.2019-0173OC |
| Citation | McGowan SE, et al. (2020) Platelet-derived Growth Factor-alpha and Neuropilin-1 Mediate Lung Fibroblast Response to Rigid Collagen Fibers. Am J Respir Cell Mol Biol 62(4):454-465 |
| abstractText | During pulmonary secondary alveolar septation, the rudimentary distal saccule subdivides by extending tissue sheets into the saccular air space, creating alveoli, which open into the alveolar duct. The sheets originate from saccular mesenchymal cells, which contain alpha-SMA (alphaSMA [ACTA2]) and abut elastic fibers (myofibroblasts [MF]), characteristics that are shared by cells that subsequently occupy the secondary septal tips. During elongation, collagen fibers are positioned to provide a scaffold for translocating septal mesenchymal cells. We hypothesized that collagen fibers direct the migration, orientation, and location of MFs during septal elongation. To address this hypothesis, we examined how electrospun collagen fibers direct the migration of fibroblasts bearing targeted deletions of PDGFRalpha (platelet-derived growth factor receptor-alpha) or Nrp1 (neuropilin-1), after their isolation from lungs that exhibit reduced secondary septation. We observed that deletion of either gene reduced Rac1 activation and the speed of migration of lung fibroblasts (LF) along electrospun fibers. The deletions did not reduce the proportion of LF that displayed collagen-binding integrins and increased the proportion of LF bearing activated beta1-integrin. LF bearing the PDGFRalpha deletion failed to localize focal adhesions over electrospun fibers, suggesting that they may not appropriately sense and respond to regionally increased stiffness near the fibers. In lungs of mice bearing the PDGFRalpha deletion, collagen fibers are delocalized from ACTA2-containing MF, and their orientation deviated from the plane of the alveolar walls. Diminished PDGFRalpha or Nrp1 reduces LF localization to stiffer regions of fibrillar collagen substrates, suggesting that signaling through these receptors enables responsiveness to regional differences in extracellular matrix rigidity. |
