Abstract: FR-PO976
Impact of IL-11 as a Renal Fibrosis Marker in CKD Using Mouse Model
Session Information
- CKD: Pathobiology - I
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2203 CKD (Non-Dialysis): Mechanisms
Authors
- Kim, Yaerim, Keimyung University School of Medicine, Daegu, Korea (the Republic of)
- Lee, Sunhwa, Kangwon National University Hospital, Chuncheon, Kangwon, Korea (the Republic of)
- Jo, Hyung Ah, Inje University Ilsan Paik Hospital, Goyang, Korea (the Republic of)
- Yoo, Kyung Don, Ulsan University Hospital, Ulsan, Korea (the Republic of)
- Paek, Jin hyuk, Keimyung University School of Medicine, Daegu, Korea (the Republic of)
- Park, Woo Yeong, Keimyung University School of Medicine, Daegu, Korea (the Republic of)
- Jin, Kyubok, Keimyung University School of Medicine, Daegu, Korea (the Republic of)
- Han, Seungyeup, Keimyung University School of Medicine, Daegu, Korea (the Republic of)
- Kim, Dong Ki, Seoul National University Hospital, Jongno-gu, Korea (the Republic of)
- Kim, Yon Su, Seoul National University Hospital, Jongno-gu, Korea (the Republic of)
- Yang, Seung Hee, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
Background
Fibrosis is a common pathophysiology of chronic kidney disease (CKD) progression, but the role of IL-11, which is highly expressed in the fibroblast remains elusive. Herein, we aimed to evaluate the role of IL-11 in the fibrosis pathway and apoptosis.
Methods
We examined the impact of IL-11 in the UUO model using B6 mouse aging 7 to 8 weeks. An in-vitro experiment was performed using primered human tubular epithelial cells (hTECs) to figure out the role of recombinant IL-11 induced fibrosis. In addition, we examined the change in the expression of phosphorylated STAT3 (pSTAT3) and IL-18 after treated recombinant TGFß (rTGFß) and rTGFß with an IL-11 blockade antibody (Ab) via fluorescence-activated cell sorting (FACS). Finally, we evaluated an impact on apoptosis using TGFß and TGFß with an IL-11 blockade Ab.
Results
Expression of IL-11 in bulk-tissue RNA-sequencing was significantly higher in the kidney lysates from the UUO model than those from sham. The levels of IL-11 expression in kidney sections from the UUO model were remarkablely correlated with the intensity of COL1 in the look-up section. Likewise, two days after treating rIL-11 with doses of 100 or 500 ng/mL in hTEC, the expression of COL1 mRNA was dose-dependently increased. rTGFß treatment significantly increased the expression of COL1, STAT3, and CXCL1 mRNA, while IL-11 blockade Ab restored the mRNA expressions of the molecules. Also, rTGFß treatment increased the expression of pSTAT3 and IL-18. IL-11 blockade Ab significantly abrogated these expressions by 60% and 33% in pSTAT3 and IL-18, respectively. Finally, the Annexin V assay revealed relevant increases in apoptotic cells treated with rTGFß, and IL-11 blockade Ab significantly attenuated the increase.
Conclusion
IL-11 has a role in the induction of fibrosis. The inhibition of IL-11 significantly attenuates the fibrotic changes, indicating that IL-11 pathway could be a treatment target for CKD progression.