DeltaNp63/BMP-7-dependent expression of matrilin-2 is involved in keratinocyte migration in response to wounding.
p63 is expressed as multiple variants including TA and DeltaN forms. Since p63-deficient mice displayed profound defects of stratified epithelia, p63 is an essential transcription factor required for epidermal morphogenesis. However, precise molecular mechanisms behind contribution of p63 to normal skin formation and healing skin wounds remained unclear. In this study, we demonstrated that DeltaNp63/BMP-7 signaling pathway modulates wound healing process through the regulation of extracellular matrix protein matrilin-2. Knocking down of DeltaNp63 in human keratinocyte HaCaT cells led to a significant reduction of matrilin-2. Intriguingly, BMP-7 which is one of DeltaNp63-target gene products, induced matrilin-2 and attenuated inhibitory effect of siRNA against DeltaNp63 on matrilin-2. Furthermore, a remarkable cell migration in response to wounding took place in DeltaNp63- or matrilin-2-knocked down cells. Taken together, our present findings indicate that DeltaNp63/BMP-7 signaling pathway modulates wound healing process through the regulation of matrilin-2.
Ichikawa
Tomoe
T
Division of Biochemistry, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuoh-ku, Chiba 260-8717, Japan.
Suenaga
Yusuke
Y
Koda
Tadayuki
T
Ozaki
Toshinori
T
Nakagawara
Akira
A
D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000502:physiology*; D064235:Matrilin Proteins; D011401:Promoter Regions, Genetic; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing / Q000235:genetics; D014947:Wounds and Injuries / Q000235:genetics / Q000378:metabolism
C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C577541:MATN2 protein, human; D064235:Matrilin Proteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins