Gclc as a Marker for Injured Distal Nephron in Ischemia-Reperfusion Induced Acute Kidney Injury
Yinzheng Li,1 Shulin Ma,1 Zheng Wang,1 Mengxia Shi,1 Rui Zeng,1– 4,* Ying Yao1,5,* 1Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Key Laboratory of Organ Transplantation, M...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2024-01-01
|
| Series: | Journal of Inflammation Research |
| Subjects: | |
| Online Access: | https://www.dovepress.com/gclc-as-a-marker-for-injured-distal-nephron-in-ischemia-reperfusion-in-peer-reviewed-fulltext-article-JIR |
| _version_ | 1797335701362049024 |
|---|---|
| author | Li Y Ma S Wang Z Shi M Zeng R Yao Y |
| author_facet | Li Y Ma S Wang Z Shi M Zeng R Yao Y |
| author_sort | Li Y |
| collection | DOAJ |
| description | Yinzheng Li,1 Shulin Ma,1 Zheng Wang,1 Mengxia Shi,1 Rui Zeng,1– 4,* Ying Yao1,5,* 1Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, 430030, People’s Republic of China; 3NHC Key Laboratory of Organ Transplantation, Wuhan, 430030, People’s Republic of China; 4Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, 430030, People’s Republic of China; 5Department of Nutrition, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying Yao; Rui Zeng, Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China, Tel +86 13720379867 ; +86 15002726366, Email yaoyingkk@126.com; zengrui@tjh.tjmu.edu.cnPurpose: The distal nephron of kidney plays a pivotal role in advancing acute kidney injury (AKI). Understanding the role of distal nephrons in AKI and identifying markers of injured distal nephrons are critical to comprehending the mechanism of renal injury and identifying novel therapeutic targets.Methods: We analyzed single-cell RNA sequencing (scRNA-seq) data from mice with AKI induced by ischemia-reperfusion (IR), unilateral ureteral obstruction (UUO), cisplatin (CP), sodium oxalate (SO) and lipopolysaccharide (LPS). Additionally, we analyzed renal transcriptomics samples for AKI. Subsequently, we validated the effectiveness of targeting the biomarker Gclc in vitro and in vivo through metabolomics and immunofluorescence.Results: The LOH-Inj and DCT-Inj subtypes were identified through scRNA-seq. Compared to normal distal nephrons, the injured distal nephrons exhibited higher levels of ferroptosis, pro-inflammation, and fibrosis. The expression of ferroptosis-related gene Gclc were high in various AKI models. Furthermore, Gclc was exclusively expressed in the distal nephron and upregulated in the injury subtype. To confirm our findings, we suppressed GCLC expression in the kidneys, resulting to aggravated IR-induced AKI. Inhibition of Gclc promoted damage to primarily renal tubular epithelial cells by promoting inflammatory infiltration, inhibiting glutathione metabolism and exacerbating oxidative stress.Conclusion: Our research findings suggest that Gclc is a potential marker for injured distal nephron.Keywords: Gclc, distal nephron, acute kidney injury, single-cell sequencing |
| first_indexed | 2024-03-08T08:42:10Z |
| format | Article |
| id | doaj.art-444aca15760544d0ad9e29d1fda8a4bb |
| institution | Directory Open Access Journal |
| issn | 1178-7031 |
| language | English |
| last_indexed | 2024-03-08T08:42:10Z |
| publishDate | 2024-01-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Journal of Inflammation Research |
| spelling | doaj.art-444aca15760544d0ad9e29d1fda8a4bb2024-02-01T17:59:28ZengDove Medical PressJournal of Inflammation Research1178-70312024-01-01Volume 1752754090066Gclc as a Marker for Injured Distal Nephron in Ischemia-Reperfusion Induced Acute Kidney InjuryLi YMa SWang ZShi MZeng RYao YYinzheng Li,1 Shulin Ma,1 Zheng Wang,1 Mengxia Shi,1 Rui Zeng,1– 4,* Ying Yao1,5,* 1Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, 430030, People’s Republic of China; 3NHC Key Laboratory of Organ Transplantation, Wuhan, 430030, People’s Republic of China; 4Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, 430030, People’s Republic of China; 5Department of Nutrition, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying Yao; Rui Zeng, Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China, Tel +86 13720379867 ; +86 15002726366, Email yaoyingkk@126.com; zengrui@tjh.tjmu.edu.cnPurpose: The distal nephron of kidney plays a pivotal role in advancing acute kidney injury (AKI). Understanding the role of distal nephrons in AKI and identifying markers of injured distal nephrons are critical to comprehending the mechanism of renal injury and identifying novel therapeutic targets.Methods: We analyzed single-cell RNA sequencing (scRNA-seq) data from mice with AKI induced by ischemia-reperfusion (IR), unilateral ureteral obstruction (UUO), cisplatin (CP), sodium oxalate (SO) and lipopolysaccharide (LPS). Additionally, we analyzed renal transcriptomics samples for AKI. Subsequently, we validated the effectiveness of targeting the biomarker Gclc in vitro and in vivo through metabolomics and immunofluorescence.Results: The LOH-Inj and DCT-Inj subtypes were identified through scRNA-seq. Compared to normal distal nephrons, the injured distal nephrons exhibited higher levels of ferroptosis, pro-inflammation, and fibrosis. The expression of ferroptosis-related gene Gclc were high in various AKI models. Furthermore, Gclc was exclusively expressed in the distal nephron and upregulated in the injury subtype. To confirm our findings, we suppressed GCLC expression in the kidneys, resulting to aggravated IR-induced AKI. Inhibition of Gclc promoted damage to primarily renal tubular epithelial cells by promoting inflammatory infiltration, inhibiting glutathione metabolism and exacerbating oxidative stress.Conclusion: Our research findings suggest that Gclc is a potential marker for injured distal nephron.Keywords: Gclc, distal nephron, acute kidney injury, single-cell sequencinghttps://www.dovepress.com/gclc-as-a-marker-for-injured-distal-nephron-in-ischemia-reperfusion-in-peer-reviewed-fulltext-article-JIRgclcdistal nephronacute kidney injurysingle-cell sequencing |
| spellingShingle | Li Y Ma S Wang Z Shi M Zeng R Yao Y Gclc as a Marker for Injured Distal Nephron in Ischemia-Reperfusion Induced Acute Kidney Injury Journal of Inflammation Research gclc distal nephron acute kidney injury single-cell sequencing |
| title | Gclc as a Marker for Injured Distal Nephron in Ischemia-Reperfusion Induced Acute Kidney Injury |
| title_full | Gclc as a Marker for Injured Distal Nephron in Ischemia-Reperfusion Induced Acute Kidney Injury |
| title_fullStr | Gclc as a Marker for Injured Distal Nephron in Ischemia-Reperfusion Induced Acute Kidney Injury |
| title_full_unstemmed | Gclc as a Marker for Injured Distal Nephron in Ischemia-Reperfusion Induced Acute Kidney Injury |
| title_short | Gclc as a Marker for Injured Distal Nephron in Ischemia-Reperfusion Induced Acute Kidney Injury |
| title_sort | gclc as a marker for injured distal nephron in ischemia reperfusion induced acute kidney injury |
| topic | gclc distal nephron acute kidney injury single-cell sequencing |
| url | https://www.dovepress.com/gclc-as-a-marker-for-injured-distal-nephron-in-ischemia-reperfusion-in-peer-reviewed-fulltext-article-JIR |
| work_keys_str_mv | AT liy gclcasamarkerforinjureddistalnephroninischemiareperfusioninducedacutekidneyinjury AT mas gclcasamarkerforinjureddistalnephroninischemiareperfusioninducedacutekidneyinjury AT wangz gclcasamarkerforinjureddistalnephroninischemiareperfusioninducedacutekidneyinjury AT shim gclcasamarkerforinjureddistalnephroninischemiareperfusioninducedacutekidneyinjury AT zengr gclcasamarkerforinjureddistalnephroninischemiareperfusioninducedacutekidneyinjury AT yaoy gclcasamarkerforinjureddistalnephroninischemiareperfusioninducedacutekidneyinjury |