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Abstract: FR-PO614

TGF-Beta 1 Signaling May Be Mediated by Lysyl Oxidase-Like 2 in Human Podocytes in Diabetic Condition

Session Information

Category: Diabetes

  • 501 Diabetes Mellitus and Obesity: Basic - Experimental

Authors

  • Lim, Beom Jin, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
  • Jeon, Nara, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
  • Choi, Hoon Young, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
Background

Lysyl oxidase-like 2 (LOXL2) is a molecule known to be related with invasive growth and metastasis of malignant neoplasm. Recently, LOXL2 has been also reported to play an important role in target organ fibrosis including heart, liver and lung. In this study, we investigated the expression of LOXL2 in human kidney and podocyte, and its contribution to the transforming growth factor beta 1 (TGF-beta1) and collagen expression in podocyte with high-glucose condition.

Methods

We evaluated the expression of LOXL2 in human kidney using immunoflurorescence staining. Real-time PCR and western blotting analysis for LOXL2 mRNA and protein expression were performed using cultured human immortalized podocytes. After fully differentiated, cultured human podocytes were exposed to high glucose (HG) for 48 hours. Lenti-virus mediated gene silencing of LOXL2 was done in human podocyte.

Results

By immunofluorescence staining, LOXL2 expression was identified in human glomerulus and was significantly increased in that with diabetic kidney disease compared with normal control. LOXL2 mRNA (2.40±0.15 vs. 1.17±0.11, P<0.05) and protein expression were significantly higher in human podocyte with HG condition than those with normal glucose condition. TGF-beta 1 mRNA expression was also increased in podocyte with HG condition (9.79±0.63 vs. 1.70±0.36, P<0.05). Gene silencing of LOXL2 significantly reduced TGF-beta mRNA and protein expression in human podocytes. Western blot analysis showed that collagen I and phosphorylated Smad2 protein expression were significantly decreased in LOXL2 knock-down podocytes.

Conclusion

Our results showed that TGF-beta 1 signaling may mediated by LOXL2 in podocytes in diabetic condition.