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...
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MDPI AG
2021-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/21/11699 |
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| 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 |
| collection | DOAJ |
| 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. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:01:42Z |
| publishDate | 2021-10-01 |
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| spelling | doaj.art-72ca142692c34aef8a7fc2d63881dc732023-11-22T20:56:34ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122211169910.3390/ijms222111699Collecting Duct-Specific CR6-Interacting Factor-1-Deletion Aggravates Renal Inflammation and Fibrosis Induced by Unilateral Ureteral ObstructionJin Young Jeong0Ki Ryang Na1Jin Ah Shin2Kwang-Sun Suh3Jwa-Jin Kim4Kang Wook Lee5Dae Eun Choi6Department of Nephrology, Chungnam National University School of Medicine, Daejeon 35015, KoreaDepartment of Nephrology, Chungnam National University School of Medicine, Daejeon 35015, KoreaDepartment of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, KoreaDepartment of Pathology, Chungnam National University School of Medicine, Daejeon 35015, KoreaDepartment of Nephrology, Chungnam National University School of Medicine, Daejeon 35015, KoreaDepartment of Nephrology, Chungnam National University School of Medicine, Daejeon 35015, KoreaDepartment of Nephrology, Chungnam National University School of Medicine, Daejeon 35015, KoreaAlthough 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.https://www.mdpi.com/1422-0067/22/21/11699CRIF1mitochondriaCre-loxpcollecting ductkidneyinflammation |
| spellingShingle | 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 International Journal of Molecular Sciences CRIF1 mitochondria Cre-loxp collecting duct kidney inflammation |
| title | 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_short | 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 |
| topic | CRIF1 mitochondria Cre-loxp collecting duct kidney inflammation |
| url | https://www.mdpi.com/1422-0067/22/21/11699 |
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