Kidney Week

Abstract: FR-PO1074

IGFBP-5/TGF-β1-Induced Cell Cross-Talk Between Endothelia and Tubular Epithelia Promotes Renal Fibrosis

Session Information

• CKD Mechanisms: Progression, Fibrosis, and Beyond
  November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2303 CKD (Non-Dialysis): Mechanisms

Authors

• Wang, Shuqiang, First Medical Center of Chinese PLA General Hospital Nephrology Institute of the Chinese People's Liberation Army, Beijing, Beijing, China

Shuqiang Wang,

• Song, Chengcheng, Beijing Electric Power Hospital, Beijing, Beijing, China

Chengcheng Song,

• Chi, Kun, First Medical Center of Chinese PLA General Hospital Nephrology Institute of the Chinese People's Liberation Army, Beijing, Beijing, China

Kun Chi,

• Zhang, Xueguang, Beijing Electric Power Hospital, Beijing, Beijing, China

Xueguang Zhang,

• Fu, Zhangning, First Medical Center of Chinese PLA General Hospital Nephrology Institute of the Chinese People's Liberation Army, Beijing, Beijing, China

Zhangning Fu,

• Geng, Xiaodong, First Medical Center of Chinese PLA General Hospital Nephrology Institute of the Chinese People's Liberation Army, Beijing, Beijing, China

Xiaodong Geng,

• Liu, Chao, First Medical Center of Chinese PLA General Hospital Nephrology Institute of the Chinese People's Liberation Army, Beijing, Beijing, China

Chao Liu,

• Cai, Guangyan, First Medical Center of Chinese PLA General Hospital Nephrology Institute of the Chinese People's Liberation Army, Beijing, Beijing, China

Guangyan Cai,

• Chen, Xiangmei, First Medical Center of Chinese PLA General Hospital Nephrology Institute of the Chinese People's Liberation Army, Beijing, Beijing, China

Xiangmei Chen,

• Hong, Quan, First Medical Center of Chinese PLA General Hospital Nephrology Institute of the Chinese People's Liberation Army, Beijing, Beijing, China

Quan Hong,

• Wu, Di, Beijing Electric Power Hospital, Beijing, Beijing, China

Di Wu,

Background

Renal fibrosis is a common pathophysiological characteristic of chronic kidney disease (CKD) for which there is no effective treatment. The mechanism of renal fibrosis is complicated and remains unclear. Our previous study revealed that Insulin-like growth factor binding protein 5 (IGFBP-5) induces glycolytic activation in ECs and ultimately aggravates renal inflammation in diabetic kidney disease (DKD).

Methods

HK-2 and HUVEC cells were included in this study. UUO and ANN model were obstructed by Wild-type, IGFBP-5^-/- and IGFBP-5^flox/flox, cre mice. IGFBP-5, TGF-β and fibrosis makers were detected to explore the mechanism of IGFBP-5 in fibrosis.

Results

We found that the serum IGFBP-5 levels were significantly increased in CKD, that IGFBP-5 was dominantly localized in vascular endothelial cells (ECs) of kidney tissue, and that IGFBP-5 deficiency relieved renal fibrosis in CKD model mice. In vitro experiments indicated that IGFBP-5 exacerbated the fibrosis phenotypic alteration of tubular epithelial cells (TECs) by the TGF-β1/p-Smad3 signaling pathway. In turn, TGF-β1 could facilitate the synthesis of IGFBP-5 in ECs. The crosstalk between TECs and ECs mediated by IGFBP-5 and TGF-β1 was confirmed in a coculture system and endothelial-specific IGFBP-5-deficient mice.

Conclusion

Renal fibrosis is exacerbated by TEC-EC cellular crosstalk through the feedback loop consisting of IGFBP-5 and TGF-β1. These findings suggest that IGFBP-5 may be a new pathogenic factor in renal fibrosis and a potential new therapeutic target in CKD.

Mechanism of the involvement of IGFBP-5 in renal fibrosis

Funding

• Government Support – Non-U.S.