Kidney Week

Abstract: FR-PO126

Targeted Ablation of Distal Cerebrospinal Fluid-Contacting Nucleus Alleviated Renal Fibrosis in CKD

Session Information

• Molecular Mechanisms of CKD - II
  October 26, 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

• Qiu, Minzi, Nanfang Hospital, Southern Medical University, Guangzhou, GUANGDONG, China

Minzi Qiu,

• Li, Jiawen, Nanfang Hospital, Southern Medical University, Guangzhou, GUANGDONG, China

Jiawen Li,

• Tan, Lishan, Nanfang Hospital, Southern Medical University, Guangzhou, GUANGDONG, China

Lishan Tan,

• Li, Aiqing, Nanfang Hospital, Southern Medical University, Guangzhou, GUANGDONG, China

Aiqing Li,

Background

The distal cerebrospinal fluid-contacting nucleus (dCSF-CNs) is thought to be a linkage between the cerebrospinal fluid and brain. The potential function of dCSF-CNs in development of CKD is poorly understood. We hypothesized that dCSF-CNs might exert a signaling transmission effect on the cascade reaction of renin-angiotensin system (RAS) in the progression of kidney injury, and that ablation of the dCSF-CNs might alleviate the local RAS and renal fibrosis in five-sixths nephrectomied (5/6Nx) rat model.

Methods

Rats were subjected to intracerebroventricular (icv) administration of artificial cerebrospinal fluid (aCSF) followed by five-sixths nephrectomied or sham operation, or icv administration of Cholera toxin subunit B conjugated with saporin (CB-SAP) for dCSF-CNs lesion before five-sixths nephrectomied. The effect of CB-SAP treatment on ablation of dCSF-CNs was confirmed via double immunofluorescence staining. The expression levels of RAS components, NOX₂ and c-fos in SFO, PVN and hippocampus, as well as the numbers of Tyrosine Hydroxilase and c-fos positive cells in RVLM were detected. The expression levels of RAS components (AGT, ACE, AT1R, ACE2, Mas receptor), NADPH oxidase (NOX₂, catalase), inflammatory cytokines (MCP-1, IL-6), fibrotic readouts (fibronectin, collagen I) in kidney were compared.

Results

Compared with 5/6Nx rats, the number of CB-labelled neurons in dCSF-CNs decreased in CB-SAP treated rats. Treatment with CB-SAP down-regulated the expression levels of RAS components (AGT, Ang II, AT1R), NADPH oxidase (NOX₂, catalase), inflammatory cytokines (MCP-1, IL-6), fibrotic readouts (fibronectin, collagen I) in rats, and up-regulated the protein levels of ACE2 and Mas receptor, compared with CKD rats. Increased numbers of Tyrosine Hydroxilase and c-fos positive cells were observed in the RVLM of 5/6Nx rats, but that were decrease under the influence of ablation of dCSF-CNs.

Conclusion

Targeted ablation of the dCSF-CNs might alleviate renal inflammation and fibrosis in the development of chronic kidney injury through inhibiting activation of inhibit the cerebral and renal RAS/ NADPH oxidase.

Funding

• Government Support - Non-U.S.