Does Arkadia contribute to TGF-β1-induced IgA expression through up-regulation of Smad signaling in IgA nephropathy?
Immunoglobulin A nephropathy (IgAN) is an immune-complex-mediated glomerulonephritis characterized by the presence of IgA deposits in mesangial and paramesangial regions. However, the exact mechanism involved in IgA deposition is still unknown. TGF-β(1) that mediates the progression of IgAN is well established as a critical IgA class (isotype) switching factor, and Smad proteins are critical intracellular mediators in the expression of TGF-β(1)-targeted genes, which suggest that TGF-β signaling has been implicated in the primary pathogenesis of IgAN. Arkadia, an E3 ubiquitin ligase, can amplify TGF-β signaling through regulating Smads degradation. When these findings are considered together, it is of interest to explore how Arkadia and Smad signaling affect TGF-β(1)-induced IgA expression in IgAN. Therefore, we propose that Arkadia could positively contribute to TGF-β(1)-induced IgA secretion through up-regulation of Smad signaling in the pathogenesis of IgAN.
Li
Xiao-Zhao
XZ
Department of Respiratory Medicine, Xiangya Hospital of Central South University, Xiangya Road No.87, 410008 Changsha, Hunan, People's Republic of China.
Feng
Jun-Tao
JT
Hu
Cheng-Ping
CP
Chen
Ze-Qi
ZQ
D000818:Animals; D005922:Glomerulonephritis, IGA / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D017578:Immunoglobulin Class Switching; D009687:Nuclear Proteins / Q000502:physiology*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*; D015854:Up-Regulation
D007070:Immunoglobulin A; D009687:Nuclear Proteins; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; C486067:RNF111 protein, human; D044767:Ubiquitin-Protein Ligases