title: Roles of SLC/CCL21 and CCR7 in human kidney for mesangial proliferation, migration, apoptosis, and tissue homeostasis.
abstract: The release of chemokines by intrinsic renal cells is an important mechanism for the regulation of leukocyte trafficking during renal inflammation. The expression of chemokine receptors by intrinsic renal cells such as mesangial cells (MC) suggests an expanded role for chemokine-chemokine receptor biology in local immunomodulation and potentially glomerular homeostasis. By immunohistochemistry we found the chemokine receptor CCR7 expressed in a mesangial pattern while the CCR7 ligand SLC/CCL21 showed a podocyte-specific expression. CCR7 expression was further characterized by RT-PCR, RNase protection assays, and FACS analysis of cultured human MC, and was found to be constitutively present. Real-time PCR of microdissected glomeruli confirmed the expression of SLC/CCL21. A functional role for CCR7 was demonstrated for human MC migration and proliferation. A protective effect of SLC/CCL21 was shown for MC survival in Fas Ab-induced apoptosis. Finally, "wound healing" was enhanced in the presence of SLC/CCL21 in an in vitro injury model. The constitutive glomerular expression of CCR7 and its ligand SLC/CCL21 in adjacent cell types of the human kidney suggests novel biological functions of this chemokine/chemokine receptor pair and a potential role in processes involved in glomerular homeostasis and regeneration.
authors.affiliation: Medical Policlinic, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Banas
authors.forename: Markus
authors.initials: M
authors.lastname: Wörnle
authors.forename: Thorsten
authors.initials: T
authors.lastname: Berger
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Nelson
authors.forename: Clemens D
authors.initials: CD
authors.lastname: Cohen
authors.forename: Matthias
authors.initials: M
authors.lastname: Kretzler
authors.forename: Jochen
authors.initials: J
authors.lastname: Pfirstinger
authors.forename: Matthias
authors.initials: M
authors.lastname: Mack
authors.forename: Martin
authors.initials: M
authors.lastname: Lipp
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Gröne
authors.forename: Detlef
authors.initials: D
authors.lastname: Schlöndorff
mesh_terms: D017209:Apoptosis; D002455:Cell Division; D002461:Cell Line, Transformed; D002470:Cell Survival; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D002633:Chemotaxis; D005920:Glomerular Mesangium / Q000166:cytology* / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D012333:RNA, Messenger / Q000096:biosynthesis; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
chemical_list: C515478:CCL21 protein, human; C515370:CCR7 protein, human; D054421:Chemokine CCL21; D019742:Chemokines, CC; D012333:RNA, Messenger; D054400:Receptors, CCR7; D019707:Receptors, Chemokine