Reticulon 4B (Nogo-B) is necessary for macrophage infiltration and tissue repair.
Blood vessel formation during ischemia and wound healing requires coordination of the inflammatory response with genes that regulate blood vessel assembly. Here we show that the reticulon family member 4B, aka Nogo-B, is upregulated in response to ischemia and is necessary for blood flow recovery secondary to ischemia and wound healing. Mice lacking Nogo-B exhibit reduced arteriogenesis and angiogenesis that are linked to a decrease in macrophage infiltration and inflammatory gene expression in vivo. Bone marrow-derived macrophages isolated from Nogo knock-out mice have reduced spreading and chemotaxis due to impaired Rac activation. Bone marrow reconstitution experiments show that Nogo in myeloid cells is necessary to promote macrophage homing and functional recovery after limb ischemia. Thus, endogenous Nogo coordinates macrophage-mediated inflammation with arteriogenesis, wound healing, and blood flow control.
Yu
Jun
J
Department of Pharmacology, Amistad Research Building, Yale University School of Medicine, New Haven, CT 06519, USA.
Fernández-Hernando
Carlos
C
Suarez
Yajaira
Y
Schleicher
Michael
M
Hao
Zhengrong
Z
Wright
Paulette L
PL
DiLorenzo
Annarita
A
Kyriakides
Themis R
TR
Sessa
William C
WC
D000818:Animals; D001783:Blood Flow Velocity / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D007249:Inflammation / Q000517:prevention & control; D007511:Ischemia / Q000503:physiopathology / Q000517:prevention & control; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D009185:Myelin Proteins / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology*; D000070798:Nogo Proteins; D012039:Regional Blood Flow / Q000502:physiology; D015854:Up-Regulation; D014945:Wound Healing / Q000502:physiology
D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603201:Rtn4 protein, mouse