Maternal hypothyroidism during pregnancy alters the function of the retinol-binding protein 4-mediated mitochondrial permeability conversion pore in the kidneys of offspring rats

OBJECTIVES To determine the role of the RBP4/PiC/SIRT3 signaling pathway in the opening of the mitochondria permeability transition pore (mPTP) in offspring rats with hypothyroidism during pregnancy. METHODS Sixty Sprague-Dawley (SD) rats were employed in this study. Pregnancy was deemed successful...

Full description

Bibliographic Details
Main Authors: Danyan Chen, Li Li, Fang Ren, Rongxi Huang, Hua Gan, Huacong Deng, Hongman Wang
Format: Article
Language:English
Published: Elsevier España 2021-01-01
Series:Clinics
Subjects:
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322021000100218&tlng=en
_version_ 1811229543021674496
author Danyan Chen
Li Li
Fang Ren
Rongxi Huang
Hua Gan
Huacong Deng
Hongman Wang
author_facet Danyan Chen
Li Li
Fang Ren
Rongxi Huang
Hua Gan
Huacong Deng
Hongman Wang
author_sort Danyan Chen
collection DOAJ
description OBJECTIVES To determine the role of the RBP4/PiC/SIRT3 signaling pathway in the opening of the mitochondria permeability transition pore (mPTP) in offspring rats with hypothyroidism during pregnancy. METHODS Sixty Sprague-Dawley (SD) rats were employed in this study. Pregnancy was deemed successful when a sperm was found in the uterus. After one week of pregnancy, offspring rats were divided into the following groups: overall hypothyroidism group (OH group), subclinical hypothyroidism group (SCH group), and normal control group (CON group). The establishment of the hypothyroidism model was confirmed when the serum thyroid stimulating hormone (TSH) levels were higher than normal value and TT4 level was within the normal range. The renal mitochondria of offspring rats were extracted on the 14th postnatal day (P14) and 35th postnatal day (P35). RESULTS At P14, no significant differences in the degree of mPTP opening and expression of phosphoric acid carrier vector (PiC) were detected between the rats in the OH group and the SCH group. However, the expression level of silent mating-type information regulation 3 homolog (SIRT3) was markedly reduced. Retinol-binding protein 4 (RBP4) expression increased in the rats from the OH group, relative to that in those from the SCH group. At P35, the degree of mPTP opening and the expression levels of PiC and RBP4 in the OH group were higher than those in the SCH group. However, SIRT3 expression in the OH group was lower than that observed in the SCH group. CONCLUSION RBP4 plays an important role in early renal mitochondrial damage and renal impairment in rats suffering from hypothyroidism during pregnancy. The RBP4/PiC/SIRT3 pathway is thus involved in the opening of the renal mPTP in offspring rats with hyperthyroidism.
first_indexed 2024-04-12T10:17:03Z
format Article
id doaj.art-9b168a642ce8488d8967e3a774647bc9
institution Directory Open Access Journal
issn 1980-5322
language English
last_indexed 2024-04-12T10:17:03Z
publishDate 2021-01-01
publisher Elsevier España
record_format Article
series Clinics
spelling doaj.art-9b168a642ce8488d8967e3a774647bc92022-12-22T03:37:11ZengElsevier EspañaClinics1980-53222021-01-017610.6061/clinics/2021/e2096Maternal hypothyroidism during pregnancy alters the function of the retinol-binding protein 4-mediated mitochondrial permeability conversion pore in the kidneys of offspring ratsDanyan Chenhttps://orcid.org/0000-0003-4473-5650Li Lihttps://orcid.org/0000-0002-3755-9030Fang Renhttps://orcid.org/0000-0002-4311-9365Rongxi Huanghttps://orcid.org/0000-0003-0072-1978Hua Ganhttps://orcid.org/0000-0001-8073-7907Huacong Denghttps://orcid.org/0000-0002-0748-8323Hongman Wanghttps://orcid.org/0000-0001-6194-8389OBJECTIVES To determine the role of the RBP4/PiC/SIRT3 signaling pathway in the opening of the mitochondria permeability transition pore (mPTP) in offspring rats with hypothyroidism during pregnancy. METHODS Sixty Sprague-Dawley (SD) rats were employed in this study. Pregnancy was deemed successful when a sperm was found in the uterus. After one week of pregnancy, offspring rats were divided into the following groups: overall hypothyroidism group (OH group), subclinical hypothyroidism group (SCH group), and normal control group (CON group). The establishment of the hypothyroidism model was confirmed when the serum thyroid stimulating hormone (TSH) levels were higher than normal value and TT4 level was within the normal range. The renal mitochondria of offspring rats were extracted on the 14th postnatal day (P14) and 35th postnatal day (P35). RESULTS At P14, no significant differences in the degree of mPTP opening and expression of phosphoric acid carrier vector (PiC) were detected between the rats in the OH group and the SCH group. However, the expression level of silent mating-type information regulation 3 homolog (SIRT3) was markedly reduced. Retinol-binding protein 4 (RBP4) expression increased in the rats from the OH group, relative to that in those from the SCH group. At P35, the degree of mPTP opening and the expression levels of PiC and RBP4 in the OH group were higher than those in the SCH group. However, SIRT3 expression in the OH group was lower than that observed in the SCH group. CONCLUSION RBP4 plays an important role in early renal mitochondrial damage and renal impairment in rats suffering from hypothyroidism during pregnancy. The RBP4/PiC/SIRT3 pathway is thus involved in the opening of the renal mPTP in offspring rats with hyperthyroidism.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322021000100218&tlng=enMaternal HypothyroidismPregnancyOffspringmPTPRBP4/PiC/SIRT3 Pathway
spellingShingle Danyan Chen
Li Li
Fang Ren
Rongxi Huang
Hua Gan
Huacong Deng
Hongman Wang
Maternal hypothyroidism during pregnancy alters the function of the retinol-binding protein 4-mediated mitochondrial permeability conversion pore in the kidneys of offspring rats
Clinics
Maternal Hypothyroidism
Pregnancy
Offspring
mPTP
RBP4/PiC/SIRT3 Pathway
title Maternal hypothyroidism during pregnancy alters the function of the retinol-binding protein 4-mediated mitochondrial permeability conversion pore in the kidneys of offspring rats
title_full Maternal hypothyroidism during pregnancy alters the function of the retinol-binding protein 4-mediated mitochondrial permeability conversion pore in the kidneys of offspring rats
title_fullStr Maternal hypothyroidism during pregnancy alters the function of the retinol-binding protein 4-mediated mitochondrial permeability conversion pore in the kidneys of offspring rats
title_full_unstemmed Maternal hypothyroidism during pregnancy alters the function of the retinol-binding protein 4-mediated mitochondrial permeability conversion pore in the kidneys of offspring rats
title_short Maternal hypothyroidism during pregnancy alters the function of the retinol-binding protein 4-mediated mitochondrial permeability conversion pore in the kidneys of offspring rats
title_sort maternal hypothyroidism during pregnancy alters the function of the retinol binding protein 4 mediated mitochondrial permeability conversion pore in the kidneys of offspring rats
topic Maternal Hypothyroidism
Pregnancy
Offspring
mPTP
RBP4/PiC/SIRT3 Pathway
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322021000100218&tlng=en
work_keys_str_mv AT danyanchen maternalhypothyroidismduringpregnancyaltersthefunctionoftheretinolbindingprotein4mediatedmitochondrialpermeabilityconversionporeinthekidneysofoffspringrats
AT lili maternalhypothyroidismduringpregnancyaltersthefunctionoftheretinolbindingprotein4mediatedmitochondrialpermeabilityconversionporeinthekidneysofoffspringrats
AT fangren maternalhypothyroidismduringpregnancyaltersthefunctionoftheretinolbindingprotein4mediatedmitochondrialpermeabilityconversionporeinthekidneysofoffspringrats
AT rongxihuang maternalhypothyroidismduringpregnancyaltersthefunctionoftheretinolbindingprotein4mediatedmitochondrialpermeabilityconversionporeinthekidneysofoffspringrats
AT huagan maternalhypothyroidismduringpregnancyaltersthefunctionoftheretinolbindingprotein4mediatedmitochondrialpermeabilityconversionporeinthekidneysofoffspringrats
AT huacongdeng maternalhypothyroidismduringpregnancyaltersthefunctionoftheretinolbindingprotein4mediatedmitochondrialpermeabilityconversionporeinthekidneysofoffspringrats
AT hongmanwang maternalhypothyroidismduringpregnancyaltersthefunctionoftheretinolbindingprotein4mediatedmitochondrialpermeabilityconversionporeinthekidneysofoffspringrats