Nicotinamide N-Methyl Transferase as a Predictive Marker of Tubular Fibrosis in CKD
Qinglin Ye,* Guiling Xu,* Haizhen Huang,* Shuting Pang, Boji Xie, Bingmei Feng, Peng Liang, Yijie Qin, Siji Li, Yin Luo, Chao Xue, Wei Li Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China*These...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2023-08-01
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| Series: | International Journal of General Medicine |
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| Online Access: | https://www.dovepress.com/nicotinamide-n-methyl-transferase-as-a-predictive-marker-of-tubular-fi-peer-reviewed-fulltext-article-IJGM |
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| author | Ye Q Xu G Huang H Pang S Xie B Feng B Liang P Qin Y Li S Luo Y Xue C Li W |
| author_facet | Ye Q Xu G Huang H Pang S Xie B Feng B Liang P Qin Y Li S Luo Y Xue C Li W |
| author_sort | Ye Q |
| collection | DOAJ |
| description | Qinglin Ye,* Guiling Xu,* Haizhen Huang,* Shuting Pang, Boji Xie, Bingmei Feng, Peng Liang, Yijie Qin, Siji Li, Yin Luo, Chao Xue, Wei Li Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Li; Chao Xue, Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Email liwei030514@126.com; xccqh@126.comPurpose: Chronic kidney disease (CKD) progression is complex. There are not standardized methods for predicting the prognosis of CKD. Nicotinamide N-methyltransferase (NNMT) has been shown to be associated with renal fibrosis. This study aimed to validate NNMT as a prognostic biomarker of progressive CKD.Patients and Methods: We explored the relationship between NNMT expression and CKD-related outcome variables using the NephroseqV5 and GEO databases. Additionally, a validation set of 37 CKD patients was enrolled to measure the correlation between NNMT expression levels and CKD outcomes. Furthermore, single-cell RNA sequencing data and the Human Protein Atlas were reanalyzed to investigate the expression specificity of NNMT in the kidney. Finally, to detect the status of NNMT expression with tubular fibrosis in vivo, we constructed a unilateral ureteral obstruction (UUO) mouse treated with an NNMT inhibitor.Results: Analyzing the datasets showed that NNMT was expressed mainly in proximal tubule compartments. And patients with high NNMT expression levels had a significantly lower overall survival rate compared to those with low NNMT expression levels (P = 0.013). NNMT was independent of prognosis factors in the multivariate Cox regression model, and the AUCs for CKD progression at 1, 3, and 5 years were 0.849, 0.775, and 0.877, respectively. Pathway enrichment analysis indicated that NNMT regulates the biological processes of tubulointerstitial fibrosis (TIF). In the validation group, NNMT levels were significantly higher in the CKD group combined with interstitial fibrosis. In vivo, NNMT was a high expression in the UUO group, peaking at postoperative day 21. Treatment with an NNMT inhibitor improved renal tubular interstitial fibrosis, and expression levels of FN, α-SMA, VIM, and TGF-β 1 were decreased compared with UUO (P < 0.05).Conclusion: NNMT was expressed mainly in tubular renal compartments, and associated with CKD prognosis. It holds potential as a diagnostic biomarker for tubular fibrosis in CKD.Graphical Abstract: Keywords: nicotinamide N-methyl transferase, tubular fibrosis, chronic kidney disease, biomarker diagnosis |
| first_indexed | 2024-03-12T16:25:20Z |
| format | Article |
| id | doaj.art-53796fe79e514cbf8ef73bde9c084ba0 |
| institution | Directory Open Access Journal |
| issn | 1178-7074 |
| language | English |
| last_indexed | 2024-03-12T16:25:20Z |
| publishDate | 2023-08-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of General Medicine |
| spelling | doaj.art-53796fe79e514cbf8ef73bde9c084ba02023-08-08T19:52:16ZengDove Medical PressInternational Journal of General Medicine1178-70742023-08-01Volume 163331334485707Nicotinamide N-Methyl Transferase as a Predictive Marker of Tubular Fibrosis in CKDYe QXu GHuang HPang SXie BFeng BLiang PQin YLi SLuo YXue CLi WQinglin Ye,* Guiling Xu,* Haizhen Huang,* Shuting Pang, Boji Xie, Bingmei Feng, Peng Liang, Yijie Qin, Siji Li, Yin Luo, Chao Xue, Wei Li Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Li; Chao Xue, Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Email liwei030514@126.com; xccqh@126.comPurpose: Chronic kidney disease (CKD) progression is complex. There are not standardized methods for predicting the prognosis of CKD. Nicotinamide N-methyltransferase (NNMT) has been shown to be associated with renal fibrosis. This study aimed to validate NNMT as a prognostic biomarker of progressive CKD.Patients and Methods: We explored the relationship between NNMT expression and CKD-related outcome variables using the NephroseqV5 and GEO databases. Additionally, a validation set of 37 CKD patients was enrolled to measure the correlation between NNMT expression levels and CKD outcomes. Furthermore, single-cell RNA sequencing data and the Human Protein Atlas were reanalyzed to investigate the expression specificity of NNMT in the kidney. Finally, to detect the status of NNMT expression with tubular fibrosis in vivo, we constructed a unilateral ureteral obstruction (UUO) mouse treated with an NNMT inhibitor.Results: Analyzing the datasets showed that NNMT was expressed mainly in proximal tubule compartments. And patients with high NNMT expression levels had a significantly lower overall survival rate compared to those with low NNMT expression levels (P = 0.013). NNMT was independent of prognosis factors in the multivariate Cox regression model, and the AUCs for CKD progression at 1, 3, and 5 years were 0.849, 0.775, and 0.877, respectively. Pathway enrichment analysis indicated that NNMT regulates the biological processes of tubulointerstitial fibrosis (TIF). In the validation group, NNMT levels were significantly higher in the CKD group combined with interstitial fibrosis. In vivo, NNMT was a high expression in the UUO group, peaking at postoperative day 21. Treatment with an NNMT inhibitor improved renal tubular interstitial fibrosis, and expression levels of FN, α-SMA, VIM, and TGF-β 1 were decreased compared with UUO (P < 0.05).Conclusion: NNMT was expressed mainly in tubular renal compartments, and associated with CKD prognosis. It holds potential as a diagnostic biomarker for tubular fibrosis in CKD.Graphical Abstract: Keywords: nicotinamide N-methyl transferase, tubular fibrosis, chronic kidney disease, biomarker diagnosishttps://www.dovepress.com/nicotinamide-n-methyl-transferase-as-a-predictive-marker-of-tubular-fi-peer-reviewed-fulltext-article-IJGMnicotinamide n-methyl transferasetubular fibrosischronic kidney diseasebiomarker diagnosis. |
| spellingShingle | Ye Q Xu G Huang H Pang S Xie B Feng B Liang P Qin Y Li S Luo Y Xue C Li W Nicotinamide N-Methyl Transferase as a Predictive Marker of Tubular Fibrosis in CKD International Journal of General Medicine nicotinamide n-methyl transferase tubular fibrosis chronic kidney disease biomarker diagnosis. |
| title | Nicotinamide N-Methyl Transferase as a Predictive Marker of Tubular Fibrosis in CKD |
| title_full | Nicotinamide N-Methyl Transferase as a Predictive Marker of Tubular Fibrosis in CKD |
| title_fullStr | Nicotinamide N-Methyl Transferase as a Predictive Marker of Tubular Fibrosis in CKD |
| title_full_unstemmed | Nicotinamide N-Methyl Transferase as a Predictive Marker of Tubular Fibrosis in CKD |
| title_short | Nicotinamide N-Methyl Transferase as a Predictive Marker of Tubular Fibrosis in CKD |
| title_sort | nicotinamide n methyl transferase as a predictive marker of tubular fibrosis in ckd |
| topic | nicotinamide n-methyl transferase tubular fibrosis chronic kidney disease biomarker diagnosis. |
| url | https://www.dovepress.com/nicotinamide-n-methyl-transferase-as-a-predictive-marker-of-tubular-fi-peer-reviewed-fulltext-article-IJGM |
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