Kidney Week

Abstract: SA-PO834

Knockdown of Cxcl10 Alleviates Renal Fibrosis in UUO Mice

Session Information

• Molecular Mechanisms of CKD - III
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 1903 CKD (Non-Dialysis): Mechanisms

Authors

• Gao, Jie, State Key Laboratory of Kidney Diseas, Chinease PLA Institute of Nephrology & Key Lab, Chinese PLA Hospital, Beijing, Beijing, China

Jie Gao,

• Wu, Lingling, State Key Laboratory of Kidney Diseas, Chinease PLA Institute of Nephrology & Key Lab, Chinese PLA Hospital, Beijing, Beijing, China

Lingling Wu,

• Chen, Xiangmei, State Key Laboratory of Kidney Diseas, Chinease PLA Institute of Nephrology & Key Lab, Chinese PLA Hospital, Beijing, Beijing, China

Xiangmei Chen,

Background

Renal fibrosis is a common pathological manifestation of almost all renal diseases, including chronic kidney disease (CKD) and acute kidney injury (AKI), which can eventually lead to end-stage renal disease (ESRD). IFN-γ-inducible protein 10 (IP-10, CXCL10) has been widely demonstrated to be involved in chemotaxis, regulation of cell growth and angiogenesis inhibition. It has been reported that CXCL10 is involved in the pathogenesis of fibrosis in a variety of human tissues. However, the underlying mechanism of CXCL10 in renal fibrosis reminds unclear.

Methods

Wildtype (CXCL10^+/+) mice and CXCL10-deficient (CXCL10^-/-) mice were used to generate the unilateral ureteral obstruction (UUO) model and sacrificed at 3, 5, 7 and 14 days after surgery. The histological changes and collagen deposition levels in kidney tissue was examined by PAS, Masson and Sirius red staining. The expression of fibrosis related proteins were examined by Western blot. The macrophage infiltration was examined by immunofluorescence of F4/80. Furthermore, the effects of CXCL10 on transforming growth factor β1 (TGF-β1)-stimulated rat renal fibroblasts was investigated in vitro.

Results

A marked increase expression of Cxcl10 mRNA and protein were observed in whole kidney tissue in UUO model. The levels of serum creatinine and urea nitrogen were significantly lower in Cxcl10^-/- mice than in Cxcl10^+/+ mice. Pathological staining results showed that the injury degree of renal tissue and the collagen deposition levels were lighter in Cxcl10^-/- mice. Western blot results showed that the expression of α-SMA, FN and Col1 in Cxcl10^-/- mice was significantly reduced compared with Cxcl10^+/+ mice. However, Interstitial F4/80-positive macrophages were unaffected by knockdown of Cxcl10. Furthermore, recombinant CXCL10 protein stimulation could obviously promote the expression of α-SMA, FN and collagen I in TGF-β1-treated NRK-49F cells.

Conclusion

Cxcl10 knockout could reduce renal injury, mitigate the deposition of collagen and inhibit renal fibrosis through promoting renal fibroblast activation in murine UUO model. These results may provide a novel insight into the mechanism and a potential therapy target of renal fibrosis.