Accelerated re-epithelialization in Dpr2-deficient mice is associated with enhanced response to TGFbeta signaling.
Members of the Dapper (Dpr)/Dact protein family are involved in the regulation of distinct signaling pathways, including TGFbeta/Nodal, canonical and noncanonical Wnt pathways. Three Dpr genes, Dpr1, Dpr2 and Dpr3, are expressed in mouse embryos and in many adult tissues; however, their in vivo functions have not been reported. In this study, we generated Dpr2-deficient mice using a gene-knockout approach. Homozygous Dpr2 knockout (Dpr2(-/-)) embryos developed normally and postnatal Dpr2(-/-) mice grew to adulthood without obvious morphological or behavioral defects. We found that Dpr2 was expressed highly in epidermal keratinocytes and in hair follicles of adult mice, and that Dpr2 deficiency resulted in accelerated re-epithelialization during cutaneous wound healing. Furthermore, we demonstrated that loss of Dpr2 function enhanced the responses of keratinocytes to TGFbeta stimulation, and that TGFbeta signals promoted adhesion to fibronectin and migration of keratinocytes, by regulating the expression of specific integrin genes. Thus, Dpr2 plays an inhibitory role in the re-epithelialization of adult skin wounds by attenuating TGFbeta signaling.
Meng
Fanwei
F
Protein Sciences Laboratory of the Ministry of Education, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, People's Republic of China.
Cheng
Xuan
X
Yang
Leilei
L
Hou
Ning
N
Yang
Xiao
X
Meng
Anming
A
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects* / Q000378:metabolism*; D020869:Gene Expression Profiling; D018390:Gene Targeting; D039564:Integrin alphaV / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects
D002352:Carrier Proteins; C517767:Dapper2 protein, mouse; D039564:Integrin alphaV; D019012:Integrin beta1; D047908:Intracellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta