Περίληψη:
The lung alveoli regenerate after surgical removal of the left lobe by
pneumonectomy (PNX). How this alveolar regrowth/regeneration is
initiated remains unknown. We found that platelets trigger lung
regeneration by supplying stromal-cell-derived factor-1 (SDF-1, also
known as CXCL12). After PNX, activated platelets stimulate SDF-1
receptors CXCR4 and CXCR7 on pulmonary capillary endothelial cells
(PCECs) to deploy the angiocrine membrane-type metalloproteinase MMP14,
stimulating alveolar epithelial cell (AEC) expansion and
neo-alveolarization. In mice lacking platelets or platelet Sdf1,
PNX-induced alveologenesis was diminished. Reciprocally, infusion of
Sdf1(+/+) but not Sdf1-deficient platelets rescued lung regeneration in
platelet-depleted mice. Endothelial-specific ablation of Cxcr4 and Cxcr7
in adult mice similarly impeded lung regeneration. Notably, mice with
endothelial-specific Mmp14 deletion exhibited impaired expansion of AECs
but not PCECs after PNX, which was not rescued by platelet infusion.
Therefore, platelets prime PCECs to initiate lung regeneration,
extending beyond their haemostatic contribution. Therapeutic targeting
of this haemo-vascular niche could enable regenerative therapy for lung
diseases.
Συγγραφείς:
Rafii, Shahin
Cao, Zhongwei
Lis, Raphael
Siempos, Ilias I.
and Chavez, Deebly
Shido, Koji
Rabbany, Sina Y.
Ding, Bi-Sen
