High sodium diet converts renal proteoglycans into pro-inflammatory mediators in rats

Ryanne S. Hijmans; Pragyi Shrestha; Kwaku A. Sarpong; Saleh Yazdani; Rana el Masri; Wilhelmina H. A. de Jong; Gerjan Navis; Romain R. Vives; Jacob van den Born

doi:10.1371/journal.pone.0178940

High sodium diet converts renal proteoglycans into pro-inflammatory mediators in rats

Ryanne S. Hijmans^*, Pragyi Shrestha, Kwaku A. Sarpong, Saleh Yazdani, Rana el Masri, Wilhelmina H. A. de Jong, Gerjan Navis, Romain R. Vives, Jacob van den Born

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Background

High dietary sodium aggravates renal disease by affecting blood pressure and by its recently shown pro-inflammatory and pro-fibrotic effects. Moreover, pro-inflammatory modification of renal heparan sulfate (HS) can induce tissue remodeling. We aim to investigate if high sodium intake in normotensive rats converts renal HS into a pro-inflammatory phenotype, able to bind more sodium and orchestrate inflammation, fibrosis and lymphangiogenesis.

Methods

Wistar rats received a normal diet for 4 weeks, or 8% NaCl diet for 2 or 4 weeks. Blood pressure was monitored, and plasma, urine and tissue collected. Tissue sodium was measured by flame spectroscopy. Renal HS and tubulo-interstitial remodeling were studied by biochemical, immunohistochemical and qRT-PCR approaches.

Results

High sodium rats showed a transient increase in blood pressure (week 1; p <0.01) and increased sodium excretion (p <0.05) at 2 and 4 weeks compared to controls. Tubulo-interstitial T-cells, myofibroblasts and mRNA levels of VCAM1, TGF-beta 1 and collagen type III significantly increased after 4 weeks (all p <0.05). There was a trend for increased macrophage infiltration and lymphangiogenesis (both p = 0.07). Despite increased dermal sodium over time (p <0.05), renal concentrations remained stable. Renal HS of high sodium rats showed increased sulfation (p = 0.05), increased L-selectin binding to HS (p <0,05), and a reduction of sulfation-sensitive anti-HS mAbs JM403 (p <0.001) and 10E4 (p <0.01). Hyaluronan expression increased under high salt conditions (p <0.01) without significant changes in the chondroitin sulfate proteoglycan versican. Statistical analyses showed that sodium-induced tissue remodeling responses partly correlated with observed HS changes.

Conclusion

We show that high salt intake by healthy normotensive rats convert renal HS into high sulfated pro-inflammatory glycans involved in tissue remodeling events, but not in increased sodium storage.

Original language	English
Article number	e0178940
Number of pages	21
Journal	PLoS ONE
Volume	12
Issue number	6
DOIs	https://doi.org/10.1371/journal.pone.0178940
Publication status	Published - 8-Jun-2017

Keywords

HEPARAN-SULFATE PROTEOGLYCANS
CHRONIC KIDNEY-DISEASE
L-SELECTIN LIGANDS
BLOOD-PRESSURE
MONOCLONAL-ANTIBODY
SALT INTAKE
GLYCOSAMINOGLYCANS
RESTRICTION
TRANSPLANTATION
BINDING

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@article{9abf9a0a859844b69345f7aa7fbb97e1,

title = "High sodium diet converts renal proteoglycans into pro-inflammatory mediators in rats",

abstract = "BackgroundHigh dietary sodium aggravates renal disease by affecting blood pressure and by its recently shown pro-inflammatory and pro-fibrotic effects. Moreover, pro-inflammatory modification of renal heparan sulfate (HS) can induce tissue remodeling. We aim to investigate if high sodium intake in normotensive rats converts renal HS into a pro-inflammatory phenotype, able to bind more sodium and orchestrate inflammation, fibrosis and lymphangiogenesis.MethodsWistar rats received a normal diet for 4 weeks, or 8% NaCl diet for 2 or 4 weeks. Blood pressure was monitored, and plasma, urine and tissue collected. Tissue sodium was measured by flame spectroscopy. Renal HS and tubulo-interstitial remodeling were studied by biochemical, immunohistochemical and qRT-PCR approaches.ResultsHigh sodium rats showed a transient increase in blood pressure (week 1; p <0.01) and increased sodium excretion (p <0.05) at 2 and 4 weeks compared to controls. Tubulo-interstitial T-cells, myofibroblasts and mRNA levels of VCAM1, TGF-beta 1 and collagen type III significantly increased after 4 weeks (all p <0.05). There was a trend for increased macrophage infiltration and lymphangiogenesis (both p = 0.07). Despite increased dermal sodium over time (p <0.05), renal concentrations remained stable. Renal HS of high sodium rats showed increased sulfation (p = 0.05), increased L-selectin binding to HS (p <0,05), and a reduction of sulfation-sensitive anti-HS mAbs JM403 (p <0.001) and 10E4 (p <0.01). Hyaluronan expression increased under high salt conditions (p <0.01) without significant changes in the chondroitin sulfate proteoglycan versican. Statistical analyses showed that sodium-induced tissue remodeling responses partly correlated with observed HS changes.ConclusionWe show that high salt intake by healthy normotensive rats convert renal HS into high sulfated pro-inflammatory glycans involved in tissue remodeling events, but not in increased sodium storage.",

keywords = "HEPARAN-SULFATE PROTEOGLYCANS, CHRONIC KIDNEY-DISEASE, L-SELECTIN LIGANDS, BLOOD-PRESSURE, MONOCLONAL-ANTIBODY, SALT INTAKE, GLYCOSAMINOGLYCANS, RESTRICTION, TRANSPLANTATION, BINDING",

author = "Hijmans, {Ryanne S.} and Pragyi Shrestha and Sarpong, {Kwaku A.} and Saleh Yazdani and {el Masri}, Rana and {de Jong}, {Wilhelmina H. A.} and Gerjan Navis and Vives, {Romain R.} and {van den Born}, Jacob",

year = "2017",

month = jun,

day = "8",

doi = "10.1371/journal.pone.0178940",

language = "English",

volume = "12",

journal = "PLoS ONE",

issn = "1932-6203",

publisher = "PUBLIC LIBRARY SCIENCE",

number = "6",

}

TY - JOUR

T1 - High sodium diet converts renal proteoglycans into pro-inflammatory mediators in rats

AU - Hijmans, Ryanne S.

AU - Shrestha, Pragyi

AU - Sarpong, Kwaku A.

AU - Yazdani, Saleh

AU - el Masri, Rana

AU - de Jong, Wilhelmina H. A.

AU - Navis, Gerjan

AU - Vives, Romain R.

AU - van den Born, Jacob

PY - 2017/6/8

Y1 - 2017/6/8

N2 - BackgroundHigh dietary sodium aggravates renal disease by affecting blood pressure and by its recently shown pro-inflammatory and pro-fibrotic effects. Moreover, pro-inflammatory modification of renal heparan sulfate (HS) can induce tissue remodeling. We aim to investigate if high sodium intake in normotensive rats converts renal HS into a pro-inflammatory phenotype, able to bind more sodium and orchestrate inflammation, fibrosis and lymphangiogenesis.MethodsWistar rats received a normal diet for 4 weeks, or 8% NaCl diet for 2 or 4 weeks. Blood pressure was monitored, and plasma, urine and tissue collected. Tissue sodium was measured by flame spectroscopy. Renal HS and tubulo-interstitial remodeling were studied by biochemical, immunohistochemical and qRT-PCR approaches.ResultsHigh sodium rats showed a transient increase in blood pressure (week 1; p <0.01) and increased sodium excretion (p <0.05) at 2 and 4 weeks compared to controls. Tubulo-interstitial T-cells, myofibroblasts and mRNA levels of VCAM1, TGF-beta 1 and collagen type III significantly increased after 4 weeks (all p <0.05). There was a trend for increased macrophage infiltration and lymphangiogenesis (both p = 0.07). Despite increased dermal sodium over time (p <0.05), renal concentrations remained stable. Renal HS of high sodium rats showed increased sulfation (p = 0.05), increased L-selectin binding to HS (p <0,05), and a reduction of sulfation-sensitive anti-HS mAbs JM403 (p <0.001) and 10E4 (p <0.01). Hyaluronan expression increased under high salt conditions (p <0.01) without significant changes in the chondroitin sulfate proteoglycan versican. Statistical analyses showed that sodium-induced tissue remodeling responses partly correlated with observed HS changes.ConclusionWe show that high salt intake by healthy normotensive rats convert renal HS into high sulfated pro-inflammatory glycans involved in tissue remodeling events, but not in increased sodium storage.

AB - BackgroundHigh dietary sodium aggravates renal disease by affecting blood pressure and by its recently shown pro-inflammatory and pro-fibrotic effects. Moreover, pro-inflammatory modification of renal heparan sulfate (HS) can induce tissue remodeling. We aim to investigate if high sodium intake in normotensive rats converts renal HS into a pro-inflammatory phenotype, able to bind more sodium and orchestrate inflammation, fibrosis and lymphangiogenesis.MethodsWistar rats received a normal diet for 4 weeks, or 8% NaCl diet for 2 or 4 weeks. Blood pressure was monitored, and plasma, urine and tissue collected. Tissue sodium was measured by flame spectroscopy. Renal HS and tubulo-interstitial remodeling were studied by biochemical, immunohistochemical and qRT-PCR approaches.ResultsHigh sodium rats showed a transient increase in blood pressure (week 1; p <0.01) and increased sodium excretion (p <0.05) at 2 and 4 weeks compared to controls. Tubulo-interstitial T-cells, myofibroblasts and mRNA levels of VCAM1, TGF-beta 1 and collagen type III significantly increased after 4 weeks (all p <0.05). There was a trend for increased macrophage infiltration and lymphangiogenesis (both p = 0.07). Despite increased dermal sodium over time (p <0.05), renal concentrations remained stable. Renal HS of high sodium rats showed increased sulfation (p = 0.05), increased L-selectin binding to HS (p <0,05), and a reduction of sulfation-sensitive anti-HS mAbs JM403 (p <0.001) and 10E4 (p <0.01). Hyaluronan expression increased under high salt conditions (p <0.01) without significant changes in the chondroitin sulfate proteoglycan versican. Statistical analyses showed that sodium-induced tissue remodeling responses partly correlated with observed HS changes.ConclusionWe show that high salt intake by healthy normotensive rats convert renal HS into high sulfated pro-inflammatory glycans involved in tissue remodeling events, but not in increased sodium storage.

KW - HEPARAN-SULFATE PROTEOGLYCANS

KW - CHRONIC KIDNEY-DISEASE

KW - L-SELECTIN LIGANDS

KW - BLOOD-PRESSURE

KW - MONOCLONAL-ANTIBODY

KW - SALT INTAKE

KW - GLYCOSAMINOGLYCANS

KW - RESTRICTION

KW - TRANSPLANTATION

KW - BINDING

U2 - 10.1371/journal.pone.0178940

DO - 10.1371/journal.pone.0178940

M3 - Article

C2 - 28594849

SN - 1932-6203

VL - 12

JO - PLoS ONE

JF - PLoS ONE

IS - 6

M1 - e0178940

ER -

High sodium diet converts renal proteoglycans into pro-inflammatory mediators in rats

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