Differential contribution of dermal resident and bone marrow-derived cells to collagen production during wound healing and fibrogenesis in mice.

Abstract

Recent studies show that bone marrow (BM)-derived cells migrating into a dermal wound promote healing by producing collagen type I. However, their contribution to the repair process has not been fully verified yet. It is also unclear whether BM-derived cells participate in dermal fibrogenesis. We have addressed these issues using transgenic mice that harbor tissue-specific enhancer/promoter sequences of α2(I) collagen gene linked to either enhanced green fluorescent protein (COL/EGFP) or the luciferase (COL/LUC) reporter gene. Following dermal excision or subcutaneous bleomycin administration, a large number of EGFP-positive collagen-producing cells appeared in the dermis of COL/EGFP reporter mice. When wild-type mice were transplanted with BM cells from transgenic COL/EGFP animals and subjected to dermal excision, no EGFP-positive BM-derived collagen-producing cells were detected throughout the repair process. Luciferase assays of dermal tissues from COL/LUC recipient mice also excluded collagen production by BM-derived cells during dermal excision healing. In contrast, a limited but significant number of CD45-positive collagen-producing cells migrated from BM following bleomycin injection. These results indicate that resident cells in the skin are the major source of de novo collagen deposition in both physiological and pathological conditions, whereas BM-derived cells participate, in part, in collagen production during dermal fibrogenesis.

• Authors: Reiichi Higashiyama, Sachie Nakao, Yayoi Shibusawa, Osamu Ishikawa, Tadashi Moro, Kenichiro Mikami, Hiroshi Fukumitsu, Yoshitaka Ueda, Kaori Minakawa, Yasuhiko Tabata, George Bou-Gharios, Yutaka Inagaki
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 131 Issue 2 Pg. 529-36 (Feb 2011) ISSN: 1523-1747 [Electronic] United States
• PMID: 20962852 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Collagen Type I
• enhanced green fluorescent protein
• Green Fluorescent Proteins
• Collagen

Topics

• Animals
• Bone Marrow Cells (cytology)
• Bone Marrow Transplantation
• Cell Movement (physiology)
• Collagen (metabolism)
• Collagen Type I
• Dermis (injuries, metabolism, pathology)
• Fibrosis (physiopathology)
• Green Fluorescent Proteins (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Models, Animal
• Promoter Regions, Genetic (physiology)
• Wound Healing (physiology)