PMID- 30524304
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 9
DP  - 2018
TI  - Targeted Ablation of Distal Cerebrospinal Fluid-Contacting Nucleus Alleviates 
      Renal Fibrosis in Chronic Kidney Disease.
PG  - 1640
LID - 10.3389/fphys.2018.01640 [doi]
LID - 1640
AB  - The potential function of distal cerebrospinal fluid-contacting nucleus 
      (dCSF-CNs) in chronic kidney disease (CKD) development is poorly understood. We 
      hypothesized that dCSF-CNs might affect the renin-angiotensin system (RAS) in 
      kidney injury progression, with dCSF-CNs ablation potentially alleviating local 
      RAS and renal fibrosis in rats after five-sixths nephrectomy (5/6Nx). Part of 
      rats were randomly administered artificial cerebrospinal fluid (aCSF) 
      intracerebroventricularly (icv), followed by 5/6Nx or sham operation; and other 
      part of rats were administered Cholera toxin B subunit conjugated with saporin 
      (CB-SAP) for dCSF-CNs lesion before 5/6Nx. The effect of CB-SAP on dCSF-CNs 
      ablation was confirmed by double immunofluorescence staining. RAS component, 
      NOX(2) and c-fos levels in the subfornical organ (SFO), hypothalamic 
      paraventricular nucleus (PVN) and hippocampus, as well as tyrosine hydroxylase 
      (TH) and c-fos positive cells in rostral ventrolateral medulla (RVLM) were 
      assessed. Next, the levels of RAS components (angiotensinogen [AGT], 
      angiotensin-converting enzyme [ACE], Ang II type 1 receptor [AT1R], 
      angiotensin-converting enzyme 2 [ACE2], and Mas receptor), NADPH oxidases (NOX(2) 
      and catalase), inflammatory cytokines (monocyte chemotactic protein 1 [MCP-1] and 
      IL-6), and fibrotic factors (fibronectin and collagen I) were assessed. Less 
      CB-labeled neurons were found in dCSF-CNs of CB-SAP-treated rats compared with 
      5/6Nx animals. Meanwhile, CB-SAP downregulated AGT, Ang II, AT1R, NOX(2), 
      catalase, MCP-1, IL-6, fibronectin, and collagen I, and upregulated ACE2 and Mas 
      receptor, compared with CKD rats. More TH and c-fos positive cells were found in 
      RVLM of 5/6Nx rats but the number decreased after dCSF-CNs ablation. Targeted 
      dCSF-CNs ablation could alleviate renal inflammation and fibrosis in chronic 
      kidney injury by inhibiting cerebral and renal RAS/NADPH oxidase.
FAU - Qiu, Minzi
AU  - Qiu M
AD  - State Key Laboratory of Organ Failure Research, National Clinical Research Center 
      for Kidney Disease, Nanfang Hospital, Southern Medical University, Guangzhou, 
      China.
FAU - Li, Jiawen
AU  - Li J
AD  - State Key Laboratory of Organ Failure Research, National Clinical Research Center 
      for Kidney Disease, Nanfang Hospital, Southern Medical University, Guangzhou, 
      China.
FAU - Tan, Lishan
AU  - Tan L
AD  - State Key Laboratory of Organ Failure Research, National Clinical Research Center 
      for Kidney Disease, Nanfang Hospital, Southern Medical University, Guangzhou, 
      China.
FAU - Zhang, Mengbi
AU  - Zhang M
AD  - State Key Laboratory of Organ Failure Research, National Clinical Research Center 
      for Kidney Disease, Nanfang Hospital, Southern Medical University, Guangzhou, 
      China.
FAU - Zhou, Guang
AU  - Zhou G
AD  - State Key Laboratory of Organ Failure Research, National Clinical Research Center 
      for Kidney Disease, Nanfang Hospital, Southern Medical University, Guangzhou, 
      China.
FAU - Zeng, Tao
AU  - Zeng T
AD  - State Key Laboratory of Organ Failure Research, National Clinical Research Center 
      for Kidney Disease, Nanfang Hospital, Southern Medical University, Guangzhou, 
      China.
FAU - Li, Aiqing
AU  - Li A
AD  - State Key Laboratory of Organ Failure Research, National Clinical Research Center 
      for Kidney Disease, Nanfang Hospital, Southern Medical University, Guangzhou, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20181121
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
PMC - PMC6262366
OTO - NOTNLM
OT  - NADPH oxidase
OT  - chronic kidney disease
OT  - dCSF-CNs
OT  - inflammation
OT  - renal fibrosis
OT  - renin-angiotensin system
OT  - sympathetic nervous system
EDAT- 2018/12/14 06:00
MHDA- 2018/12/14 06:01
PMCR- 2018/11/21
CRDT- 2018/12/08 06:00
PHST- 2018/05/25 00:00 [received]
PHST- 2018/10/30 00:00 [accepted]
PHST- 2018/12/08 06:00 [entrez]
PHST- 2018/12/14 06:00 [pubmed]
PHST- 2018/12/14 06:01 [medline]
PHST- 2018/11/21 00:00 [pmc-release]
AID - 10.3389/fphys.2018.01640 [doi]
PST - epublish
SO  - Front Physiol. 2018 Nov 21;9:1640. doi: 10.3389/fphys.2018.01640. eCollection 
      2018.