title: Excessive activation of the TLR9/TGF-β1/PDGF-B pathway in the peripheral blood of patients with systemic lupus erythematosus.
abstract: Our aim is to study the existence of the TLR9/TGF-β1/PDGF-B pathway in healthy humans and patients with systemic lupus erythematosus (SLE), and to explore its possible involvement in the pathogenesis of lupus nephritis (LN).
  
  
  
  Protein levels of the cytokines were detected by ELISA. mRNA levels of the cytokines were analyzed by real-time PCR. MTT assay was used to test the proliferation of mesangial cells under different treatments.
  
  
  
  Compared to healthy controls (NControl= 56), levels of Toll-like receptor (TLR)9, transforming growth factor (TGF)-β1, and platelet-derived growth factor B (PDGF-B) were increased significantly in the peripheral blood of SLE patients (NSLE= 112). Significant correlations between the levels of TLR9, TGF-β1, and PDGF-B were observed in both healthy controls and SLE patients. The levels of TGF-β1 and PDGF-B were greatly enhanced by TLR9 activation in primary cell cultures. The proliferation of mesangial cells induced by the plasma of SLE patients was significantly higher than that induced by healthy controls; PDGF-B was involved in this process. The protein levels of PDGF-B homodimer correlated with the levels of urine protein in SLE patients with LN (NLN=38).
  
  
  
  The TLR9/TGF-β1/PDGF-B pathway exists in humans and can be excessively activated in SLE patients. High levels of PDGF-B may result in overproliferation of mesangial cells in the kidney that are involved in the development of glomerulonephritis and LN. Further studies are necessary to identify TLR9, TGF-β1, and PDGF-B as new therapeutic targets to prevent the development of glomerulonephritis and LN.
authors.affiliation: Institute of Translational Medicine, the First Hospital, Jilin University, Changchun, 130061, China.|Department of Rheumatology and Immunology, the First Hospital, Jilin University, Changchun, 130021, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Institute of Translational Medicine, the First Hospital, Jilin University, Changchun, 130061, China.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Yang
authors.affiliation: Institute of Translational Medicine, the First Hospital, Jilin University, Changchun, 130061, China.
authors.forename: Kuo
authors.initials: K
authors.lastname: Wang
authors.affiliation: Shanghai Wisdom Chemical Research Co. Ltd., Shanghai, 201203, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Institute of Translational Medicine, the First Hospital, Jilin University, Changchun, 130061, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Song
authors.affiliation: Institute of Translational Medicine, the First Hospital, Jilin University, Changchun, 130061, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Diao
authors.affiliation: Department of Rheumatology and Immunology, the First Hospital, Jilin University, Changchun, 130021, China. jlujzy@aliyun.com.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Institute of Translational Medicine, the First Hospital, Jilin University, Changchun, 130061, China. gcheng@mednet.ucla.edu.|Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA, 90095, USA. gcheng@mednet.ucla.edu.
authors.forename: Genhong
authors.initials: G
authors.lastname: Cheng
authors.affiliation: Institute of Translational Medicine, the First Hospital, Jilin University, Changchun, 130061, China. zhuanhuawang@163.com.
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Wang
mesh_terms: D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood; D008181:Lupus Nephritis / Q000097:blood*; D008297:Male; D050527:Mesangial Cells / Q000378:metabolism; D008875:Middle Aged; D020574:Proto-Oncogene Proteins c-sis / Q000097:blood*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D051217:Toll-Like Receptor 9 / Q000097:blood*; D053773:Transforming Growth Factor beta1 / Q000097:blood*
chemical_list: D020574:Proto-Oncogene Proteins c-sis; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D053773:Transforming Growth Factor beta1
keywords: Lupus nephritis; Systemic lupus erythematosus; Toll-like receptor 9