title: Sublytic C5b-9 complexes induce proliferative changes of glomerular mesangial cells in rat Thy-1 nephritis through TRAF6-mediated PI3K-dependent Akt1 activation.
abstract: The proliferation of glomerular mesangial cells (GMCs) and secretion of extracellular matrix (ECM) in rat Thy-1 nephritis (Thy-1N), resembling human mesangioproliferative glomerulonephritis (MsPGN), have been studied for many years, but the mechanisms, especially the role of signalling pathway activation and its regulation in GMCs triggered by sublytic C5b-9 complexes in Thy-1N rats remain largely unclear. In the study, the proliferation of GMCs and production of ECM as well as the role of PI3K/Akt and its regulation, both in GMCs induced by sublytic C5b-9 (in vitro) and in the renal tissues of rats with Thy-1N (in vivo), were determined and the results revealed that GMCs proliferation and ECM secretion, both in vitro and in vivo, were notably increased, and that PI3K/Akt1 activation and its regulation, such as TNF receptor-associated factor 6 (TRAF6)-mediated Akt1 ubiquitination and PI3K-dependent Akt1 phosphorylation, were involved in the process of Thy-1N induction. On the other hand, silence of the TRAF6, PI3K or Akt1 genes could obviously diminish the proliferative damages and urinary protein secretion of Thy-1N rats. Together, these data implicated that sublytic C5b-9 complexes in Thy-1N rats could promote GMCs proliferation and ECM production through TRAF6-mediated PI3K-dependent Akt1 activation, in which the ubiquitination and phosphorylation of the Akt1 signal molecule played an important role in the initiation and development of the proliferative changes in the rats with Thy-1N.
authors: Department of Immunology and Lab of Immunopathology, Nanjing Medical University, People's Republic of China.
authors: Wen
authors: W
authors: Qiu
authors: Yan
authors: Y
authors: Zhang
authors: Xiaomei
authors: X
authors: Liu
authors: Jianbo
authors: J
authors: Zhou
authors: Yan
authors: Y
authors: Li
authors: Ying
authors: Y
authors: Zhou
authors: Kai
authors: K
authors: Shan
authors: Mei
authors: M
authors: Xia
authors: Nan
authors: N
authors: Che
authors: Xuefeng
authors: X
authors: Feng
authors: Dan
authors: D
authors: Zhao
authors: Yingwei
authors: Y
authors: Wang
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D015938:Complement Membrane Attack Complex / Q000494:pharmacology*; D020868:Gene Silencing; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007518:Isoantibodies / Q000494:pharmacology; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009393:Nephritis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis* / Q000235:genetics; D011507:Proteinuria / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics / Q000378:metabolism*; D018800:Thy-1 Antigens / Q000276:immunology; D054875:Ubiquitination / Q000187:drug effects
chemical_list: D015938:Complement Membrane Attack Complex; D007518:Isoantibodies; D048029:TNF Receptor-Associated Factor 6; D018800:Thy-1 Antigens; C035678:anti-Thy antibody; D019869:Phosphatidylinositol 3-Kinases; C494920:Akt1 protein, rat; D051057:Proto-Oncogene Proteins c-akt