title: In vivo interstitial migration of primitive macrophages mediated by JNK-matrix metalloproteinase 13 signaling in response to acute injury.
abstract: Interstitial cell migration through extracellular matrix is a hallmark of the inflammation response, tumor invasion, and metastasis. We have established a stable zebrafish transgenic line expressing enhanced GFP under the lysozyme C promoter for visualizing and measuring primitive macrophage migration in vivo. We show that tissue-resident primitive macrophages migrate rapidly through extracellular matrix to the site of acute injury induced by tail transection. Mechanistically, the specific inhibition of JNK, but not p38 and ERK, dramatically abolished the chemotactic migration in a dose-dependent manner, suppressing the trauma-induced recruitment of phosphorylated C-Jun transcription factor to proximal AP-1 sites in the promoter of matrix metalloproteinase 13 (mmp13), a gene specifically expressed in primitive macrophages during embryogenesis and required for the interstitial migration. Furthermore, dexamethasone suppressed the trauma-induced JNK phosphorylation and macrophage migration accompanied by simultaneous up-regulation of mkp-1, a well-known phosphatase capable of inactivating phosphorylated JNK. The results indicate that the JNK-Mmp13 signaling pathway plays an essential role in regulating the innate immune cell migration in response to severe injury in vivo.
authors.affiliation: Laboratory of Development and Diseases and State Key Laboratory for Medical Genomics and Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xue-Tao
authors.initials: XT
authors.lastname: Bai
authors.forename: Kang-Yong
authors.initials: KY
authors.lastname: Zhu
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
authors.forename: Min
authors.initials: M
authors.lastname: Deng
authors.forename: Huang-Ying
authors.initials: HY
authors.lastname: Le
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Fu
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhu
authors.forename: A Thomas
authors.initials: AT
authors.lastname: Look
authors.forename: John
authors.initials: J
authors.lastname: Kanki
authors.forename: Zhu
authors.initials: Z
authors.lastname: Chen
authors.forename: Sai-Juan
authors.initials: SJ
authors.lastname: Chen
authors.forename: Ting Xi
authors.initials: TX
authors.lastname: Liu
mesh_terms: D000208:Acute Disease; D000818:Animals; D030801:Animals, Genetically Modified; D002465:Cell Movement / Q000187:drug effects; D054638:Dual Specificity Phosphatase 1 / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology; D007422:Intestines / Q000166:cytology* / Q000196:embryology / Q000201:enzymology* / Q000293:injuries; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism*; D015394:Molecular Structure; D011401:Promoter Regions, Genetic / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation / Q000235:genetics; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D047428:Protein Kinase Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D054638:Dual Specificity Phosphatase 1; D053509:Matrix Metalloproteinase 13