A new role of substance P as an injury-inducible messenger for mobilization of CD29(+) stromal-like cells.
Tissue injury may create a specific microenvironment for inducing the systemic participation of stromal-like cells in the repair process. Here we show that substance P is an injury-inducible factor that acts early in the wound healing process to induce CD29(+) stromal-like cell mobilization. Likewise, mobilization of such cells also occurs in uninjured mice, rats and rabbits if substance P is intravenously injected. Upon further characterization these substance P-mobilized CD29(+) cells were found to be similar to stromal cells from a number of connective tissues, including bone marrow (that is, bone marrow stromal cells, or BMSCs). Both substance P injection and transfusion of autologously derived substance P-mobilized CD29(+) cells from uninjured rabbits accelerated wound healing in an alkali burn model. Also, epithelial engraftment of the transfused cells into the injured tissue occurred during the wound healing. Finally, using human BMSCs as a test population, we show that substance P stimulates transmigration, cell proliferation, activation of the extracellular signal-related kinases (Erk) 1 and 2 and nuclear translocation of beta-catenin in vitro. This finding highlights a previously undescribed function of substance P as a systemically acting messenger of injury and a mobilizer of CD29(+) stromal-like cells to participate in wound healing.
Hong
Hyun Sook
HS
Department of Genetic Engineering, College of Life Science and Graduate School of Biotechnology, Kyung Hee University, 1 Seochun-dong, Kiheung-ku, Yong In 441-706, Korea.
Lee
Jungsun
J
Lee
EunAh
E
Kwon
Young Sam
YS
Lee
Eunkyung
E
Ahn
Woosung
W
Jiang
Mei Hua
MH
Kim
Jae Chan
JC
Son
Youngsook
Y
D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D005131:Eye Injuries / Q000628:therapy; D019650:Hematopoietic Stem Cell Mobilization; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D019012:Integrin beta1 / Q000502:physiology*; D007375:Interleukin-1 / Q000235:genetics; D051379:Mice; D039904:Pluripotent Stem Cells / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D012038:Regeneration / Q000502:physiology; D017154:Stromal Cells / Q000502:physiology*; D013373:Substance P / Q000235:genetics / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014945:Wound Healing / Q000502:physiology*; D051176:beta Catenin / Q000502:physiology
C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019012:Integrin beta1; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D051176:beta Catenin; D013373:Substance P