Role of CREB in vasoactive intestinal peptide-mediated wound healing in human bronchial epithelial cells.
Vasoactive intestinal peptide (VIP) is one of the most important sensory neuropeptides in respiratory system. We previously reported that VIP enhances wound healing and proliferation of human bronchial epithelial cells (HBECs), and these effects are mediated by intracellular signaling molecules such as protein kinase A (PKA), protein kinase C (PKC), Calmodulin (CaM), and extracellular signal-regulated kinase (ERK). In the present study, we further investigated the role of cAMP Response Element Binding Protein (CREB) in VIP-promoted protective effects in mechanical-damaged HBECs. VIP-mediated wound healing and cell proliferation in HBECs was inhibited by CREB antisense oligonucleotides (ASO) in a time-dependent manner. VIP increased the CREB DNA binding activity and expression of the p-CREB that were inhibited by VIP receptor antagonist. Increased CREB DNA binding activity and expression of the p-CREB were also partially inhibited by PKA and ERK inhibitors. These results suggest that the VIP-mediated wound repair of HBECs is associated with activation of CREB via PKA and ERK dependent pathway.
Guan
Cha-Xiang
CX
Department of Physiology, Central South University Xiangya Medical School, Changsha, Hunan 410078, China. gcxdzd91@163.com
Cui
Yan-Ru
YR
Sun
Guo-Ying
GY
Yu
Fang
F
Tang
Chun-Yan
CY
Li
Yun-Chao
YC
Liu
Hui-Jun
HJ
Fang
Xiang
X
D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000473:pathology; D002460:Cell Line; D049109:Cell Proliferation; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D018005:Receptors, Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*; D014945:Wound Healing
D017362:Cyclic AMP Response Element-Binding Protein; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide; D017868:Cyclic AMP-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases