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Kidney Week

Abstract: TH-PO922

Latent Transforming Growth Factor Beta Binding Protein 4 (LTBP4) Deficiency Attenuates the Severity of Renal Fibrosis

Session Information

Category: CKD (Non-Dialysis)

  • 1903 CKD (Non-Dialysis): Mechanisms


  • Su, Chi-Ting, National Taiwan University Hospital, Taipei, Taiwan
  • Huang, Jenq-wen, National Taiwan University Hospital, Taipei, Taiwan

Transforming growth factor beta (TGFβ) has been proved to be related to fibrosis including renal fibrosis that is characterized by the accumulation of extra-cellular matrix (ECM). LTBPs are recognized to direct and facilitate TGFβ action through several mechanisms. Moreover, the complexity of progression of renal injury remains vague. The intensive investigation of the mechanism will lead us understand the potential therapy for patients. We propose that ltbp4 can be an essential regulatory factor in renal injury because of its variety.


To create renal fibrosis model, we did unilateral ureteral ligation (UUO) in mice and check echocardiography to exam the cardiac contractility every other weeks. Ltbp4S-/- mice were used to investigate the potential regulatory role of ltbp4 in renal fibrosis related to TGFβ signaling. Protein and RNA extraction were collected for real-time PCR, RNA-Seq, and down-stream signaling, protein-protein interaction, and proteomics analysis.


Up-regulation of ltbp4 had been noted 14 days after UUO at gene and protein levels. The major area of ltbp4 expression in the renal tissue was around proximal tubules areas and glomerular area was absent of expression. In addition, α-smooth muscle actin (SMA), kidney Injury Molecule-1 (KIM-1) and monocyte chemoattractant protein-1 (MCP-1) expression at mRNA level increased significantly following the UUO surgery but in ltbp4S-/- mice, the expression had been drastically reduced. KIM-1, pSMAD2, pEKR and platelet-derived growth factor receptors beta (Pdgfrb) were increasing at protein levels after renal injury. Immunofluorescence staining studies revealed less expression of Pdgfrb, F4/80 and collagen I in ltbp4S-/- mice. TGFB receptors are speculated to be interacted with ltbp4, leading to abnormal down-stream signaling in ltbp4-deficient environments.


Reduced macrophage infiltration had been noted in renal injury tissue among post-UUO surgery ltbp4S-/- mice. Moreover, renal myofibroblasts expressed less Pdgfrb. In ltbp4-deficient environment, the severity of inflammation and renal injury induced by UUO can be reduced.


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