Endothelial cells regulate alveolar morphogenesis by constructing basement membranes acting as a scaffold for myofibroblasts

Haruko Watanabe-Takano (), Katsuhiro Kato, Eri Oguri-Nakamura, Tomohiro Ishii, Koji Kobayashi, Takahisa Murata, Koichiro Tsujikawa, Takaki Miyata, Yoshiaki Kubota, Yasuyuki Hanada, Koichi Nishiyama, Tetsuro Watabe, Reinhard Fässler, Hirotaka Ishii, Naoki Mochizuki and Shigetomo Fukuhara ()
Additional contact information
Haruko Watanabe-Takano: Nippon Medical School
Katsuhiro Kato: Nagoya University
Eri Oguri-Nakamura: Nippon Medical School
Tomohiro Ishii: Nippon Medical School
Koji Kobayashi: University of Tokyo
Takahisa Murata: University of Tokyo
Koichiro Tsujikawa: Nagoya University
Takaki Miyata: Nagoya University
Yoshiaki Kubota: Keio University School of Medicine
Yasuyuki Hanada: Nagoya University
Koichi Nishiyama: University of Miyazaki
Tetsuro Watabe: Tokyo Medical and Dental University
Reinhard Fässler: Max Planck Institute of Biochemistry
Hirotaka Ishii: Nippon Medical School
Naoki Mochizuki: National Cerebral and Cardiovascular Center Research Institute
Shigetomo Fukuhara: Nippon Medical School

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract Alveologenesis is a spatially coordinated morphogenetic event, during which alveolar myofibroblasts surround the terminal sacs constructed by epithelial cells and endothelial cells (ECs), then contract to form secondary septa to generate alveoli in the lungs. Recent studies have demonstrated the important role of alveolar ECs in this morphogenetic event. However, the mechanisms underlying EC-mediated alveologenesis remain unknown. Herein, we show that ECs regulate alveologenesis by constructing basement membranes (BMs) acting as a scaffold for myofibroblasts to induce septa formation through activating mechanical signaling. Rap1, a small GTPase of the Ras superfamily, is known to stimulate integrin-mediated cell adhesions. EC-specific Rap1-deficient (Rap1iECKO) mice exhibit impaired septa formation and hypo-alveolarization due to the decreased mechanical signaling in myofibroblasts. In Rap1iECKO mice, ECs fail to stimulate integrin β1 to recruit Collagen type IV (Col-4) into BMs required for myofibroblast-mediated septa formation. Consistently, EC-specific integrin β1-deficient mice show hypo-alveolarization, defective mechanical signaling in myofibroblasts, and disorganized BMs. These data demonstrate that alveolar ECs promote integrin β1-mediated Col-4 recruitment in a Rap1-dependent manner, thereby constructing BMs acting as a scaffold for myofibroblasts to induce mechanical signal-mediated alveologenesis. Thus, this study unveils a mechanism of organ morphogenesis mediated by ECs through intrinsic functions.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-45910-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45910-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-45910-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().