Mast cells are dispensable for normal and activin-promoted wound healing and skin carcinogenesis.
The growth and differentiation factor activin A is a key regulator of tissue repair, inflammation, fibrosis, and tumorigenesis. However, the cellular targets, which mediate the different activin functions, are still largely unknown. In this study, we show that activin increases the number of mature mast cells in mouse skin in vivo. To determine the relevance of this finding for wound healing and skin carcinogenesis, we mated activin transgenic mice with CreMaster mice, which are characterized by Cre recombinase-mediated mast cell eradication. Using single- and double-mutant mice, we show that loss of mast cells neither affected the stimulatory effect of overexpressed activin on granulation tissue formation and reepithelialization of skin wounds nor its protumorigenic activity in a model of chemically induced skin carcinogenesis. Furthermore, mast cell deficiency did not alter wounding-induced inflammation and new tissue formation or chemically induced angiogenesis and tumorigenesis in mice with normal activin levels. These findings reveal that mast cells are not major targets of activin during wound healing and skin cancer development and also argue against nonredundant functions of mast cells in wound healing and skin carcinogenesis in general.
Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology Zurich, 8093 Zürich, Switzerland;
Maria
M
Antsiferova
Caroline
C
Martin
Marcel
M
Huber
Thorsten B
TB
Feyerabend
Anja
A
Förster
Karin
K
Hartmann
Hans-Reimer
HR
Rodewald
Daniel
D
Hohl
Sabine
S
Werner
D015127:9,10-Dimethyl-1,2-benzanthracene; D028341:Activins / Q000008:administration & dosage / Q000172:deficiency / Q000494:pharmacology*; D000818:Animals; D002273:Carcinogens; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000139:chemically induced / Q000473:pathology*; D002633:Chemotaxis / Q000187:drug effects; D005260:Female; D006801:Humans; D015552:Injections, Intralesional; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000473:pathology; D020556:Neutrophil Infiltration; D010212:Papilloma / Q000098:blood supply / Q000139:chemically induced / Q000473:pathology*; D019009:Proto-Oncogene Proteins c-kit / Q000172:deficiency; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012867:Skin / Q000293:injuries / Q000473:pathology; D012878:Skin Neoplasms / Q000098:blood supply / Q000139:chemically induced / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate; D014945:Wound Healing / Q000187:drug effects*
D002273:Carcinogens; D011994:Recombinant Proteins; C422405:activin A; D028341:Activins; D015127:9,10-Dimethyl-1,2-benzanthracene; D019009:Proto-Oncogene Proteins c-kit; D013755:Tetradecanoylphorbol Acetate