Dataset Information

Salt-induced phosphoproteomic changes in the subfornical organ in rats with chronic kidney disease.

ABSTRACT:

Objectives

Subfornical organ (SFO) is vital in chronic kidney disease (CKD) progression caused by high salt levels. The current study investigated the effects of high salt on phosphoproteomic changes in SFO in CKD rats.

Methods

5/6 nephrectomized rats were fed a normal-salt diet (0.4%) (NC group) or a high-salt diet (4%) (HC group) for three weeks, while sham-operated rats were fed a normal-salt diet (0.4%) (NS group). For phosphoproteomic analysis of SFO in different groups, TiO₂ enrichment, isobaric tags for relative and absolute quantification (iTRAQ) labeling, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used.

Results

There were 6808 distinct phosphopeptides found, which corresponded to 2661 phosphoproteins. NC group had 168 upregulated and 250 downregulated phosphopeptides compared to NS group. Comparison to NC group, HC group had 154 upregulated and 124 downregulated phosphopeptides. Growth associated protein 43 (GAP43) and heat shock protein 27 (Hsp27) were significantly upregulated phosphoproteins and may protect against high-salt damage. Differential phosphoproteins with tight functional connection were synapse proteins and microtubule-associated proteins, implying that high-salt diet disrupted brain's structure and function. Furthermore, differential phosphoproteins in HC/NC comparison group were annotated to participate in GABAergic synapse signaling pathway and aldosterone synthesis and secretion, which attenuated inhibitory neurotransmitter effects and increased sympathetic nerve activity (SNA).

Discussion

This large scale phosphoproteomic profiling of SFO sheds light on how salt aggravates CKD via the central nervous system.

SUBMITTER: Wang X

PROVIDER: S-EPMC9888458 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Salt-induced phosphoproteomic changes in the subfornical organ in rats with chronic kidney disease.

Wang Xin X Wang Huizhen H Li Jiawen J Li Lanying L Wang Yifan Y Li Aiqing A

Renal failure 20231201 1

<h4>Objectives</h4>Subfornical organ (SFO) is vital in chronic kidney disease (CKD) progression caused by high salt levels. The current study investigated the effects of high salt on phosphoproteomic changes in SFO in CKD rats.<h4>Methods</h4>5/6 nephrectomized rats were fed a normal-salt diet (0.4%) (NC group) or a high-salt diet (4%) (HC group) for three weeks, while sham-operated rats were fed a normal-salt diet (0.4%) (NS group). For phosphoproteomic analysis of SFO in different groups, TiO< ...[more]

PMID: 36715439

Similar Datasets

Project description:Diet-induced models of chronic kidney disease (CKD) offer several advantages, including clinical relevance and animal welfare, compared with surgical models. Oxalate is a plant-based, terminal toxic metabolite that is eliminated by the kidneys through glomerular filtration and tubular secretion. An increased load of dietary oxalate leads to supersaturation, calcium oxalate crystal formation, renal tubular obstruction, and eventually CKD. Dahl-Salt-Sensitive (SS) rats are a common strain used to study hypertensive renal disease; however, the characterization of other diet-induced models on this background would allow for comparative studies of CKD within the same strain. In the present study, we hypothesized that SS rats on a low-salt, oxalate rich diet would have increased renal injury and serve as novel, clinically relevant and reproducible CKD rat models. Ten-week-old male SS rats were fed either 0.2% salt normal chow (SS-NC) or a 0.2% salt diet containing 0.67% sodium oxalate (SS-OX) for five weeks.Real-time PCR demonstrated an increased expression of inflammatory marker interleukin-6 (IL-6) (p < 0.0001) and fibrotic marker Timp-1 metalloproteinase (p < 0.0001) in the renal cortex of SS-OX rat kidneys compared with SS-NC. The immunohistochemistry of kidney tissue demonstrated an increase in CD-68 levels, a marker of macrophage infiltration in SS-OX rats (p < 0.001). In addition, SS-OX rats displayed increased 24 h urinary protein excretion (UPE) (p < 0.01) as well as significant elevations in plasma Cystatin C (p < 0.01). Furthermore, the oxalate diet induced hypertension (p < 0.05). A renin-angiotensin-aldosterone system (RAAS) profiling (via liquid chromatography-mass spectrometry; LC-MS) in the SS-OX plasma showed significant (p < 0.05) increases in multiple RAAS metabolites including angiotensin (1-5), angiotensin (1-7), and aldosterone. The oxalate diet induces significant renal inflammation, fibrosis, and renal dysfunction as well as RAAS activation and hypertension in SS rats compared with a normal chow diet. This study introduces a novel diet-induced model to study hypertension and CKD that is more clinically translatable and reproducible than the currently available models.

Project description:BackgroundEvidence indicates that reducing dietary salt may reduce the incidence of heart disease and delay decline in kidney function in people with chronic kidney disease (CKD). This is an update of a review first published in 2015.ObjectivesTo evaluate the benefits and harms of altering dietary salt for adults with CKD.Search methodsWe searched the Cochrane Kidney and Transplant Register of Studies up to 6 October 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.Selection criteriaRandomised controlled trials comparing two or more levels of salt intake in adults with any stage of CKD.Data collection and analysisTwo authors independently assessed studies for eligibility, conducted risk of bias evaluation and evaluated confidence in the evidence using GRADE. Results were summarised using random effects models as risk ratios (RR) for dichotomous outcomes or mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI).Main resultsWe included 21 studies (1197 randomised participants), 12 in the earlier stages of CKD (779 randomised participants), seven in dialysis (363 randomised participants) and two in post-transplant (55 randomised participants). Selection bias was low in seven studies, high in one and unclear in 13. Performance and detection biases were low in four studies, high in two, and unclear in 15. Attrition and reporting biases were low in 10 studies, high in three and unclear in eight. Because duration of the included studies was too short (1 to 36 weeks) to test the effect of salt restriction on endpoints such as death, cardiovascular events or CKD progression, changes in salt intake on blood pressure and other secondary risk factors were examined. Reducing salt by mean -73.51 mmol/day (95% CI -92.76 to -54.27), equivalent to 4.2 g or 1690 mg sodium/day, reduced systolic/diastolic blood pressure by -6.91/-3.91 mm Hg (95% CI -8.82 to -4.99/-4.80 to -3.02; 19 studies, 1405 participants; high certainty evidence). Albuminuria was reduced by 36% (95% CI 26 to 44) in six studies, five of which were carried out in people in the earlier stages of CKD (MD -0.44, 95% CI -0.58 to -0.30; 501 participants; high certainty evidence). The evidence is very uncertain about the effect of lower salt intake on weight, as the weight change observed (-1.32 kg, 95% CI -1.94 to -0.70; 12 studies, 759 participants) may have been due to fluid volume, lean tissue, or body fat. Lower salt intake may reduce extracellular fluid volume in the earlier stages of CKD (-0.87 L, 95% CI -1.17 to -0.58; 3 studies; 187 participants; low certainty evidence). The evidence is very uncertain about the effect of lower salt intake on reduction in antihypertensive dose (RR 2.45, 95% CI 0.98 to 6.08; 8 studies; 754 participants). Lower salt intake may lead to symptomatic hypotension (RR 6.70, 95% CI 2.40 to 18.69; 6 studies; 678 participants; moderate certainty evidence). Data were sparse for other types of adverse events.Authors' conclusionsWe found high certainty evidence that salt reduction reduced blood pressure in people with CKD, and albuminuria in people with earlier stage CKD in the short-term. If such reductions could be maintained long-term, this effect may translate to clinically significant reductions in CKD progression and cardiovascular events. Research into the long-term effects of sodium-restricted diet for people with CKD is warranted.

Dataset Information

Salt-induced phosphoproteomic changes in the subfornical organ in rats with chronic kidney disease.

Objectives

Methods

Results

Discussion

Publications

Salt-induced phosphoproteomic changes in the subfornical organ in rats with chronic kidney disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets