title: Phosphoinositide 3-kinase/protein kinase B/periostin mediated platelet-derived growth factor-induced cell proliferation and extracellular matrix production in lupus nephritis.
abstract: In the present study, the effect and mechanism of periostin on renal proliferation and extracellular matrix accumulation of lupus mice were investigated. MRL /lpr mice, known as lupus mice, were revealed to show enhanced periostin, proliferating cell nuclear antigen (PCNA), and extracellular matrix accumulation in the kidney accompanied by increased serum platelet-derived growth factor (PDGF). Again, cultured mouse mesangial cells (MMCs) were treated with PDGF, then periostin, and PCNA and secreted fibronectin were detected. The results showed that intracellular periostin and PCNA were respectively enhanced by 2.691 and 2.308 times in PDGF-treated MMC cells at 6 h after stimulation. In addition, secreted fibronectin was increased by 1.442 times. Next, the transfection of periostin shRNA vector in PDGF-stimulated MMC cells effectively suppressed periostin, PCNA and secreted fibronectin by 45.27%, 47.75%, and 39.95%, compared with PDGF-stimulated cells transfected with control vector. Furthermore, it was found that PDGF increased the expression of phospho-Akt (Ser 473) from 30 min to 6 h in MMCs. LY294002 effectively inhibited phospho-Akt (Ser 473) expression caused by PDGF stimulation. Then, periostin, PCNA, and fibronectin were respectively decreased by 69.61%, 46.00%, and 46.20%. In the end, phosphoinositide 3-kinase/protein kinase B/periostin was suggested to mediate PDGF-induced cell proliferation and extracellular matrix production in lupus nephritis.
authors: 1 Department of Pathology, Hebei Medical University, Shijiazhuang 050017, China.|2 Department of Pediatrics, the 2nd Affiliated Hospital of Hebei Medical University, Shijiazhuang 050017, China.
authors: Xue
authors: X
authors: Zhao
authors: 1 Department of Pathology, Hebei Medical University, Shijiazhuang 050017, China.
authors: Jun
authors: J
authors: Hao
authors: 1 Department of Pathology, Hebei Medical University, Shijiazhuang 050017, China.
authors: Huijun
authors: H
authors: Duan
authors: 2 Department of Pediatrics, the 2nd Affiliated Hospital of Hebei Medical University, Shijiazhuang 050017, China.
authors: Zanhua
authors: Z
authors: Rong
authors: 1 Department of Pathology, Hebei Medical University, Shijiazhuang 050017, China.
authors: Fan
authors: F
authors: Li
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000502:physiology*; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008181:Lupus Nephritis / Q000473:pathology*; D050527:Mesangial Cells / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D015815:Cell Adhesion Molecules; D002867:Chromones; D005353:Fibronectins; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010982:Platelet-Derived Growth Factor; D018809:Proliferating Cell Nuclear Antigen; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; C512835:POSTN protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
keywords: Periostin; extracellular matrix; lupus nephritis; phosphoinositide 3-kinase/protein kinase B; platelet-derived growth factor; proliferating cell nuclear antigen