Epithelial protein lost in neoplasm modulates platelet-derived growth factor-mediated adhesion and motility of mesangial cells.
Mesangial cell migration, regulated by several growth factors, is crucial after glomerulopathy and during glomerular development. Directional migration requires the establishment of a polarized cytoskeletal arrangement, a process regulated by coordinated actin dynamics and focal adhesion turnover at the peripheral ruffles in migrating cells. Here we found high expression of the actin cross-linking protein EPLIN (epithelial protein lost in neoplasm) in mesangial cells. EPLIN was localized in mesangial angles, which consist of actin-containing microfilaments extending underneath the capillary endothelium, where they attach to the glomerular basement membrane. In cultured mesangial cells, EPLIN was localized in peripheral actin bundles at focal adhesions and formed a protein complex with paxillin. The MEK-ERK (extracellular signal-regulated kinase) cascade regulated EPLIN-paxillin interaction and induced translocalization of EPLIN from focal adhesion sites to peripheral ruffles. Knockdown of EPLIN in mesangial cells enhanced platelet-derived growth factor-induced focal adhesion disassembly and cell migration. Furthermore, EPLIN expression was decreased in mesangial proliferative nephritis in rodents and humans in vivo. These results shed light on the coordinated actin remodeling in mesangial cells during restorative remodeling. Thus, changes in expression and localization of cytoskeletal regulators underlie phenotypic changes in mesangial cells in glomerulonephritis.
Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Haruko
H
Tsurumi
Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Yutaka
Y
Harita
Department of Anatomy, Juntendo University School of Medicine, Tokyo, Japan.
Hidetake
H
Kurihara
Division of Cell Signaling, Fujii Memorial Institute of Medical Sciences, The University of Tokushima, Tokushima, Japan.
Hidetaka
H
Kosako
Department of Molecular Biology, Yokohama City University School of Medicine, Kanagawa, Japan.
Kenji
K
Hayashi
Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Atsuko
A
Matsunaga
Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Yuko
Y
Kajiho
Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Shoichiro
S
Kanda
Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Kenichiro
K
Miura
Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Takashi
T
Sekine
Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Akira
A
Oka
Department of Pediatric Nephrology, Tokyo Women's Medical University, School of Medicine, Tokyo, Japan.
Kiyonobu
K
Ishizuka
Department of Pediatric Nephrology, Tokyo Women's Medical University, School of Medicine, Tokyo, Japan.
Shigeru
S
Horita
Department of Pediatric Nephrology, Tokyo Women's Medical University, School of Medicine, Tokyo, Japan.
Motoshi
M
Hattori
Department of Biochemistry, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Seisuke
S
Hattori
1] Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan [2] National Center for Child Health and Development, Tokyo, Japan.
Takashi
T
Igarashi
D000199:Actins / Q000378:metabolism; D000293:Adolescent; D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D002648:Child; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D005922:Glomerulonephritis, IGA / Q000378:metabolism; D015432:Glomerulonephritis, Membranoproliferative / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D050527:Mesangial Cells / Q000502:physiology*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D051419:Paxillin / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018800:Thy-1 Antigens / Q000378:metabolism
D000199:Actins; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D051419:Paxillin; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D018800:Thy-1 Antigens; C403263:LIMA1 protein, human; C000598072:Lima1 protein, rat; C498862:Acta2 protein, rat