title: Defocused low-energy shock wave activates adipose tissue-derived stem cells in vitro via multiple signaling pathways.
abstract: We found defocused low-energy shock wave (DLSW) could be applied in regenerative medicine by activating mesenchymal stromal cells. However, the possible signaling pathways that participated in this process remain unknown. In the present study, DLSW was applied in cultured rat adipose tissue-derived stem cells (ADSCs) to explore its effect on ADSCs and the activated signaling pathways.
  
  
  
  After treating with DLSW, the cellular morphology and cytoskeleton of ADSCs were observed. The secretions of ADSCs were detected. The expressions of ADSC surface antigens were analyzed using flow cytometry. The expressions of proliferating cell nuclear antigen and Ki67 were analyzed using western blot. The expression of CXCR2 and the migrations of ADSCs in vitro and in vivo were detected. The phosphorylation of selected signaling pathways with or without inhibitors was also detected.
  
  
  
  DLSW did not change the morphology and phenotype of ADSCs, and could promote the secretion, proliferation and migration of ADSCs. The phosphorylation levels were significantly higher in mitogen-activated protein kinases (MAPK) pathway, phosphoinositide 3-kinase (PI-3K)/AKT pathway and nuclear factor-kappa B (NF-κB) signaling pathway but not in Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Furthermore, ADSCs were not activated by DLSW after adding the inhibitors of these pathways simultaneously.
  
  
  
  Our results demonstrated for the first time that DLSW could activate ADSCs through MAPK, PI-3K/AKT and NF-κB signaling pathways. Combination of DLSW and agonists targeting these pathways might improve the efficacy of ADSCs in regenerative medicine in the future.
authors.affiliation: Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Xu
authors.affiliation: Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Muwen
authors.initials: M
authors.lastname: Wang
authors.affiliation: Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.affiliation: Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Peking University Third Hospital, Beijing, China; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Xunbo
authors.initials: X
authors.lastname: Jin
authors.affiliation: Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China; Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, California, USA. Electronic address: zhyhope77@163.com.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D053612:Janus Kinases / Q000378:metabolism; D019394:Ki-67 Antigen / Q000096:biosynthesis; D020935:MAP Kinase Signaling System / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D023063:Receptors, Interleukin-8B / Q000096:biosynthesis; D044968:Regenerative Medicine; D000069453:Ultrasonic Waves
chemical_list: D016207:Cytokines; D019394:Ki-67 Antigen; D016328:NF-kappa B; D018809:Proliferating Cell Nuclear Antigen; D023063:Receptors, Interleukin-8B; D019869:Phosphatidylinositol 3-Kinases; D053612:Janus Kinases
keywords: Janus kinase; adipose tissue-derived stem cells; cell proliferation; cell signaling; defocused low-energy shock wave; mitogen-activated protein kinase; regenerative medicine