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Kidney Week

Abstract: TH-PO470

LOXL4 Promotes Renal Fibrosis via Triggering Col1 Production

Session Information

  • CKD: Mechanisms - I
    November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Zhu, Saiya, Shanghai Tongji Hospital, Shanghai, China
  • Yu, Chen, Shanghai Tongji Hospital, Shanghai, China
Background

Renal fibrosis characterized by excessive deposition of extracellular matrix (ECM) represents a feature of end stage of kidney disease. ECM consists of collagen ,fibronectin, elastin and so on. Over crosslinking of extracellular matrix acts as a key role in the process of fibrosis. Lysyl oxidase (LOXs) facilitates the crosslinking of collagen and elastin. Lysyl oxidase-like protein 4(LOXL4) is the latest member of the LOXs family. Till now, there is no report about the pathogenesis of LOXL4 during renal fibrosis. The aim of the current study is to uncover the role of LOXL4 in renal fibrosis.

Methods

Human renal specimens were obtained from renal biopsy and normal renal tissues adjacent to renal cancer after nephrectomized kidneys. Fibrosis in the kidney specimens was assessed by Masson's trichrome staining, and LOXL4 expression was examined by using IHC staining. We used unilateral ureteral ligation (UUO) kidney in vivo and used a cell line of rat fibroblast (NRK-49F) in vitro to demonstrate the underlying mechanism of LOXL4 with renal fibrosis by realtime-PCR and western blot analysis. We investigated the biological role of LOXL4 after over-expression or silencing its expression in NRK-49F.

Results

LOXL4 deposited in the fibrotic renal tissue in patients with diabetic nephropathy,which were significantly higher compared with that in renal tissues adjacent to renal cancer after nephrectomized kidneys and minimal changed disease. Compared with sham group, the expressions of LOXL4 and Col1 in the kidney of UUO group were extremely upregulated (p<0.05, n=5). TGF-β1 significantly increased the expression of LOXL4 and Col1 (p<0.05, n=5) in NRK-49F. After transfecting with LOXL4 overexpression plasmid, the Col1 expression was significantly increased. There was sharply reduction of Col1 in NRK-49F cells after transfected with LOXL4 siRNA.

Conclusion

LOXL4 was significantly increased in human and rat fibrosis, and TGF-β1/Smads promotes the expression of LOXL4.This indicates that LOXL4 is closely related to the renal fibrosis.

LOXL4 expression in human kidney tissues