title: Kidney injury molecule-1 is involved in the chemotactic migration of mesenchymal stem cells.
abstract: A better understanding of the organ specific factors that regulate the migration of mesenchymal stem cells (MSCs) into the target organ is essential for optimization of strategies to improve the repair after injury. In the present study, we showed that the kidney injury molecule-1 (KIM-1), a well-known kidney-specific biomarker, enhanced the in vitro migration capacity of MSCs as a potent kidney-specific chemo-attractant or an inducer. The in vitro roles were verified by migration assay using KIM1-PK1 cell lines, the mouse proximal tubular epithelial cells (mPTEs) and recombinant human KIM-1 proteins (rhKIM-1). Immunofluorescence staining displayed specific ectodomain binding of KIM-1 on the surface of MSCs. Upregulation of chemokine receptor type 4 (CXCR4) protein when treated with tumor necrosis factor alpha (TNF-α) was shown. The effect of KIM-1 on migration of MSCs was augmented by TNF-α pretreatment in a dose-dependent manner, and reduced by AMD3100, an antagonist of CXCR4. These results suggest that KIM-1 is a potential chemo-ligand of CXCR4 and may play an important role in kidney-specific migration of MSCs via interaction between KIM-1 and CXCR4.
authors.affiliation: Stem Cell Institute-KNU, Kangwon National University, Chuncheon, 200-701, South Korea, vethouse2000@gmail.com.
authors.forename: Kyung-Mee
authors.initials: KM
authors.lastname: Park
authors.forename: Hyun-Suk
authors.initials: HS
authors.lastname: Nam
authors.forename: Pankaj Kumar
authors.initials: PK
authors.lastname: Teotia
authors.forename: Kamal Hany
authors.initials: KH
authors.lastname: Hussein
authors.forename: Seok-Ho
authors.initials: SH
authors.lastname: Hong
authors.forename: Jung-Im
authors.initials: JI
authors.lastname: Yun
authors.forename: Heung-Myong
authors.initials: HM
authors.lastname: Woo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001596:Benzylamines; D015153:Blotting, Western; D002465:Cell Movement / Q000502:physiology*; D002633:Chemotaxis / Q000502:physiology*; D000080027:Cyclams; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D000072596:Hepatitis A Virus Cellular Receptor 1; D006571:Heterocyclic Compounds; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D001596:Benzylamines; C527276:CXCR4 protein, human; D000080027:Cyclams; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D006571:Heterocyclic Compounds; D008562:Membrane Glycoproteins; D019718:Receptors, CXCR4; D011991:Receptors, Virus; D014409:Tumor Necrosis Factor-alpha; C088327:plerixafor