Collecting Duct-Specific CR6-Interacting Factor-1-Deletion Aggravates Renal Inflammation and Fibrosis Induced by Unilateral Ureteral Obstruction

Although inflammation and fibrosis, which are key mechanisms of chronic kidney disease, are associated with mitochondrial damage, little is known about the effects of mitochondrial damage on the collecting duct in renal inflammation and fibrosis. To generate collecting duct-specific mitochondrial in...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jin Young Jeong, Ki Ryang Na, Jin Ah Shin, Kwang-Sun Suh, Jwa-Jin Kim, Kang Wook Lee, Dae Eun Choi
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	CRIF1 mitochondria Cre-loxp collecting duct kidney inflammation Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/72ca142692c34aef8a7fc2d63881dc73
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:72ca142692c34aef8a7fc2d63881dc73
record_format	dspace
spelling	oai:doaj.org-article:72ca142692c34aef8a7fc2d63881dc732021-11-11T17:09:54ZCollecting Duct-Specific CR6-Interacting Factor-1-Deletion Aggravates Renal Inflammation and Fibrosis Induced by Unilateral Ureteral Obstruction10.3390/ijms2221116991422-00671661-6596https://doaj.org/article/72ca142692c34aef8a7fc2d63881dc732021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11699https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Although inflammation and fibrosis, which are key mechanisms of chronic kidney disease, are associated with mitochondrial damage, little is known about the effects of mitochondrial damage on the collecting duct in renal inflammation and fibrosis. To generate collecting duct-specific mitochondrial injury mouse models, CR6-interacting factor-1 (CRIF1) <sup>flox/flox</sup> mice were bred with Hoxb7-Cre mice. We evaluated the phenotype of these mice. To evaluate the effects on unilateral ureteral obstruction (UUO)-induced renal injury, we divided the mice into the following four groups: a CRIF1<sup>flox/flox</sup> (wild-type (WT)) group, a CRIF1<sup>flox/flox</sup>-Hob7 Cre (CRIF1-KO) group, a WT-UUO group, and a CRIF1-KO UUO group. We evaluated the blood and urine chemistries, inflammatory and fibrosis markers, light microscopy, and electron microscopy of the kidneys. The inhibition of <i>Crif1</i> mRNA in mIMCD cells reduced oxygen consumption and membrane potential. No significant differences in blood and urine chemistries were observed between WT and CRIF1-KO mice. In UUO mice, monocyte chemoattractant protein-1 and osteopontin expression, number of F4/80 positive cells, transforming growth factor-β and α-smooth muscle actin staining, and Masson’s trichrome staining were significantly higher in the kidneys of CRIF1-KO mice compared with the kidneys of WT mice. In sham mice, urinary 8-hydroxydeoxyguanosine (8-OHDG) was higher in CRIF1-KO mice than in WT mice. Moreover, CRIF1-KO sham mice had increased 8-OHDG-positive cell recruitment compared with WT-sham mice. CRIF1-KO-UUO kidneys had increased recruitment of 8-OHDG-positive cells compared with WT-UUO kidneys. In conclusion, collecting duct-specific mitochondrial injury increased oxidative stress. Oxidative stress associated with mitochondrial damage may aggravate UUO-induced renal injury.Jin Young JeongKi Ryang NaJin Ah ShinKwang-Sun SuhJwa-Jin KimKang Wook LeeDae Eun ChoiMDPI AGarticleCRIF1mitochondriaCre-loxpcollecting ductkidneyinflammationBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11699, p 11699 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	CRIF1 mitochondria Cre-loxp collecting duct kidney inflammation Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	CRIF1 mitochondria Cre-loxp collecting duct kidney inflammation Biology (General) QH301-705.5 Chemistry QD1-999 Jin Young Jeong Ki Ryang Na Jin Ah Shin Kwang-Sun Suh Jwa-Jin Kim Kang Wook Lee Dae Eun Choi Collecting Duct-Specific CR6-Interacting Factor-1-Deletion Aggravates Renal Inflammation and Fibrosis Induced by Unilateral Ureteral Obstruction
description	Although inflammation and fibrosis, which are key mechanisms of chronic kidney disease, are associated with mitochondrial damage, little is known about the effects of mitochondrial damage on the collecting duct in renal inflammation and fibrosis. To generate collecting duct-specific mitochondrial injury mouse models, CR6-interacting factor-1 (CRIF1) <sup>flox/flox</sup> mice were bred with Hoxb7-Cre mice. We evaluated the phenotype of these mice. To evaluate the effects on unilateral ureteral obstruction (UUO)-induced renal injury, we divided the mice into the following four groups: a CRIF1<sup>flox/flox</sup> (wild-type (WT)) group, a CRIF1<sup>flox/flox</sup>-Hob7 Cre (CRIF1-KO) group, a WT-UUO group, and a CRIF1-KO UUO group. We evaluated the blood and urine chemistries, inflammatory and fibrosis markers, light microscopy, and electron microscopy of the kidneys. The inhibition of <i>Crif1</i> mRNA in mIMCD cells reduced oxygen consumption and membrane potential. No significant differences in blood and urine chemistries were observed between WT and CRIF1-KO mice. In UUO mice, monocyte chemoattractant protein-1 and osteopontin expression, number of F4/80 positive cells, transforming growth factor-β and α-smooth muscle actin staining, and Masson’s trichrome staining were significantly higher in the kidneys of CRIF1-KO mice compared with the kidneys of WT mice. In sham mice, urinary 8-hydroxydeoxyguanosine (8-OHDG) was higher in CRIF1-KO mice than in WT mice. Moreover, CRIF1-KO sham mice had increased 8-OHDG-positive cell recruitment compared with WT-sham mice. CRIF1-KO-UUO kidneys had increased recruitment of 8-OHDG-positive cells compared with WT-UUO kidneys. In conclusion, collecting duct-specific mitochondrial injury increased oxidative stress. Oxidative stress associated with mitochondrial damage may aggravate UUO-induced renal injury.
format	article
author	Jin Young Jeong Ki Ryang Na Jin Ah Shin Kwang-Sun Suh Jwa-Jin Kim Kang Wook Lee Dae Eun Choi
author_facet	Jin Young Jeong Ki Ryang Na Jin Ah Shin Kwang-Sun Suh Jwa-Jin Kim Kang Wook Lee Dae Eun Choi
author_sort	Jin Young Jeong
title	Collecting Duct-Specific CR6-Interacting Factor-1-Deletion Aggravates Renal Inflammation and Fibrosis Induced by Unilateral Ureteral Obstruction
title_short	Collecting Duct-Specific CR6-Interacting Factor-1-Deletion Aggravates Renal Inflammation and Fibrosis Induced by Unilateral Ureteral Obstruction
title_full	Collecting Duct-Specific CR6-Interacting Factor-1-Deletion Aggravates Renal Inflammation and Fibrosis Induced by Unilateral Ureteral Obstruction
title_fullStr	Collecting Duct-Specific CR6-Interacting Factor-1-Deletion Aggravates Renal Inflammation and Fibrosis Induced by Unilateral Ureteral Obstruction
title_full_unstemmed	Collecting Duct-Specific CR6-Interacting Factor-1-Deletion Aggravates Renal Inflammation and Fibrosis Induced by Unilateral Ureteral Obstruction
title_sort	collecting duct-specific cr6-interacting factor-1-deletion aggravates renal inflammation and fibrosis induced by unilateral ureteral obstruction
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/72ca142692c34aef8a7fc2d63881dc73
work_keys_str_mv	AT jinyoungjeong collectingductspecificcr6interactingfactor1deletionaggravatesrenalinflammationandfibrosisinducedbyunilateralureteralobstruction AT kiryangna collectingductspecificcr6interactingfactor1deletionaggravatesrenalinflammationandfibrosisinducedbyunilateralureteralobstruction AT jinahshin collectingductspecificcr6interactingfactor1deletionaggravatesrenalinflammationandfibrosisinducedbyunilateralureteralobstruction AT kwangsunsuh collectingductspecificcr6interactingfactor1deletionaggravatesrenalinflammationandfibrosisinducedbyunilateralureteralobstruction AT jwajinkim collectingductspecificcr6interactingfactor1deletionaggravatesrenalinflammationandfibrosisinducedbyunilateralureteralobstruction AT kangwooklee collectingductspecificcr6interactingfactor1deletionaggravatesrenalinflammationandfibrosisinducedbyunilateralureteralobstruction AT daeeunchoi collectingductspecificcr6interactingfactor1deletionaggravatesrenalinflammationandfibrosisinducedbyunilateralureteralobstruction
_version_	1718432184196399104

Collecting Duct-Specific CR6-Interacting Factor-1-Deletion Aggravates Renal Inflammation and Fibrosis Induced by Unilateral Ureteral Obstruction

Ejemplares similares