Cargando…

Small intestine resection increases oxalate and citrate transporter expression and calcium oxalate crystal formation in rat hyperoxaluric kidneys

Short bowel (SB) increases the risk of kidney stones. However, the underlying mechanism is unclear. Here, we examined how SB affected renal oxalate and citrate handlings for in vivo hyperoxaluric rats and in vitro tubular cells. SB was induced by small intestine resection in male Wistar rats. Sham-o...

Descripción completa

Detalles Bibliográficos
Autores principales: Tseng, Yi-Shiou, Wu, Wen-Bin, Chen, Yun, Lo Yang, Feili, Ma, Ming-Chieh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557498/
https://www.ncbi.nlm.nih.gov/pubmed/33006369
http://dx.doi.org/10.1042/CS20200973
_version_ 1783594434170978304
author Tseng, Yi-Shiou
Wu, Wen-Bin
Chen, Yun
Lo Yang, Feili
Ma, Ming-Chieh
author_facet Tseng, Yi-Shiou
Wu, Wen-Bin
Chen, Yun
Lo Yang, Feili
Ma, Ming-Chieh
author_sort Tseng, Yi-Shiou
collection PubMed
description Short bowel (SB) increases the risk of kidney stones. However, the underlying mechanism is unclear. Here, we examined how SB affected renal oxalate and citrate handlings for in vivo hyperoxaluric rats and in vitro tubular cells. SB was induced by small intestine resection in male Wistar rats. Sham-operated controls had no resection. After 7 days of recovery, the rats were divided into control, SB (both fed with distilled water), ethylene glycol (EG), and SB+EG (both fed with 0.75% EG for hyperoxaluric induction) groups for 28 days. We collected the plasma, 24 h of urine, kidney, and intestine tissues for analysis. Hypocitraturia was found and persisted up to 28 days for the SB group. Hypocalcemia and high plasma parathyroid hormone (PTH) levels were found in the 28-day SB rats. SB aggravated EG-mediated oxalate nephropathy by fostering hyperoxaluria and hypocitraturia, and increasing the degree of supersaturation and calcium oxalate (CaOx) crystal deposition. These effects were associated with renal up-regulations of the oxalate transporter solute carrier family 26 (Slc26)a6 and citrate transporter sodium-dependent dicarboxylate cotransporter-1 (NaDC-1) but not Slc26a2. The effects of PTH on the SB kidneys were then examined in NRK-52E tubular cells. Recombinant PTH attenuated oxalate-mediated cell injury and up-regulated NaDC-1 via protein kinase A (PKA) activation. PTH, however, showed no additive effects on oxalate-induced Slc26a6 and NaDC-1 up-regulation. Together, these results demonstrated that renal NaDC-1 upregulation-induced hypocitraturia weakened the defense against Slc26a6-mediated hyperoxaluria in SB kidneys for excess CaOx crystal formation. Increased tubular NaDC-1 expression caused by SB relied on PTH.
format Online
Article
Text
id pubmed-7557498
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Portland Press Ltd.
record_format MEDLINE/PubMed
spelling pubmed-75574982020-10-21 Small intestine resection increases oxalate and citrate transporter expression and calcium oxalate crystal formation in rat hyperoxaluric kidneys Tseng, Yi-Shiou Wu, Wen-Bin Chen, Yun Lo Yang, Feili Ma, Ming-Chieh Clin Sci (Lond) Gastrointestinal, Renal & Hepatic Systems Short bowel (SB) increases the risk of kidney stones. However, the underlying mechanism is unclear. Here, we examined how SB affected renal oxalate and citrate handlings for in vivo hyperoxaluric rats and in vitro tubular cells. SB was induced by small intestine resection in male Wistar rats. Sham-operated controls had no resection. After 7 days of recovery, the rats were divided into control, SB (both fed with distilled water), ethylene glycol (EG), and SB+EG (both fed with 0.75% EG for hyperoxaluric induction) groups for 28 days. We collected the plasma, 24 h of urine, kidney, and intestine tissues for analysis. Hypocitraturia was found and persisted up to 28 days for the SB group. Hypocalcemia and high plasma parathyroid hormone (PTH) levels were found in the 28-day SB rats. SB aggravated EG-mediated oxalate nephropathy by fostering hyperoxaluria and hypocitraturia, and increasing the degree of supersaturation and calcium oxalate (CaOx) crystal deposition. These effects were associated with renal up-regulations of the oxalate transporter solute carrier family 26 (Slc26)a6 and citrate transporter sodium-dependent dicarboxylate cotransporter-1 (NaDC-1) but not Slc26a2. The effects of PTH on the SB kidneys were then examined in NRK-52E tubular cells. Recombinant PTH attenuated oxalate-mediated cell injury and up-regulated NaDC-1 via protein kinase A (PKA) activation. PTH, however, showed no additive effects on oxalate-induced Slc26a6 and NaDC-1 up-regulation. Together, these results demonstrated that renal NaDC-1 upregulation-induced hypocitraturia weakened the defense against Slc26a6-mediated hyperoxaluria in SB kidneys for excess CaOx crystal formation. Increased tubular NaDC-1 expression caused by SB relied on PTH. Portland Press Ltd. 2020-10 2020-10-13 /pmc/articles/PMC7557498/ /pubmed/33006369 http://dx.doi.org/10.1042/CS20200973 Text en © 2020 The Author(s). https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY-NC-ND).
spellingShingle Gastrointestinal, Renal & Hepatic Systems
Tseng, Yi-Shiou
Wu, Wen-Bin
Chen, Yun
Lo Yang, Feili
Ma, Ming-Chieh
Small intestine resection increases oxalate and citrate transporter expression and calcium oxalate crystal formation in rat hyperoxaluric kidneys
title Small intestine resection increases oxalate and citrate transporter expression and calcium oxalate crystal formation in rat hyperoxaluric kidneys
title_full Small intestine resection increases oxalate and citrate transporter expression and calcium oxalate crystal formation in rat hyperoxaluric kidneys
title_fullStr Small intestine resection increases oxalate and citrate transporter expression and calcium oxalate crystal formation in rat hyperoxaluric kidneys
title_full_unstemmed Small intestine resection increases oxalate and citrate transporter expression and calcium oxalate crystal formation in rat hyperoxaluric kidneys
title_short Small intestine resection increases oxalate and citrate transporter expression and calcium oxalate crystal formation in rat hyperoxaluric kidneys
title_sort small intestine resection increases oxalate and citrate transporter expression and calcium oxalate crystal formation in rat hyperoxaluric kidneys
topic Gastrointestinal, Renal & Hepatic Systems
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557498/
https://www.ncbi.nlm.nih.gov/pubmed/33006369
http://dx.doi.org/10.1042/CS20200973
work_keys_str_mv AT tsengyishiou smallintestineresectionincreasesoxalateandcitratetransporterexpressionandcalciumoxalatecrystalformationinrathyperoxalurickidneys
AT wuwenbin smallintestineresectionincreasesoxalateandcitratetransporterexpressionandcalciumoxalatecrystalformationinrathyperoxalurickidneys
AT chenyun smallintestineresectionincreasesoxalateandcitratetransporterexpressionandcalciumoxalatecrystalformationinrathyperoxalurickidneys
AT loyangfeili smallintestineresectionincreasesoxalateandcitratetransporterexpressionandcalciumoxalatecrystalformationinrathyperoxalurickidneys
AT mamingchieh smallintestineresectionincreasesoxalateandcitratetransporterexpressionandcalciumoxalatecrystalformationinrathyperoxalurickidneys