Cutting edge: Calcium/Calmodulin-dependent protein kinase type IV is essential for mesangial cell proliferation and lupus nephritis.
Renal involvement in systemic lupus erythematosus remains a major cause of morbidity and mortality. Although immune parameters that instigate renal damage have been characterized, their link to local processes, which execute tissue damage, is poorly understood. Using genetic-deletion and pharmacological-inhibition approaches, we demonstrated that calcium/calmodulin-dependent protein kinase type IV, which contributes to altered cytokine production in systemic lupus erythematosus patients, controls spontaneous and platelet-derived growth factor-stimulated mesangial cell proliferation and promotes IL-6 production through AP-1. Our studies identified calcium/calmodulin-dependent protein kinase type IV as a valuable treatment target for lupus nephritis and point out the importance of local kidney factors in the expression of tissue damage that, if properly targeted, should enhance clinical benefit and limit toxicity.
Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Kunihiro
K
Ichinose
Thomas
T
Rauen
Yuang-Taung
YT
Juang
Katalin
K
Kis-Toth
Masayuki
M
Mizui
Tomohiro
T
Koga
George C
GC
Tsokos
D000818:Animals; D015153:Blotting, Western; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4 / Q000378:metabolism*; D049109:Cell Proliferation; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D008181:Lupus Nephritis / Q000201:enzymology* / Q000473:pathology*; D050527:Mesangial Cells / Q000201:enzymology* / Q000473:pathology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015850:Interleukin-6; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; C517685:Camk4 protein, mouse