KITLG Promotes Glomerular Endothelial Cell Injury in Diabetic Nephropathy by an Autocrine Effect
Diabetic nephropathy (DN) is an increasing threat to human health. The impact of hyperglycemia or its metabolites, advanced glycation end-products (AGEs), on glomerular endothelial cells (GECs) and their pathophysiologic mechanisms are not well explored. Our results reveal that AGEs increased the ex...
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/19/11723 |
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| author | Jiun-Chi Huang Szu-Chia Chen Wei-An Chang Wei-Wen Hung Ping-Hsun Wu Ling-Yu Wu Jer-Ming Chang Ya-Ling Hsu Yi-Chun Tsai |
| author_facet | Jiun-Chi Huang Szu-Chia Chen Wei-An Chang Wei-Wen Hung Ping-Hsun Wu Ling-Yu Wu Jer-Ming Chang Ya-Ling Hsu Yi-Chun Tsai |
| author_sort | Jiun-Chi Huang |
| collection | DOAJ |
| description | Diabetic nephropathy (DN) is an increasing threat to human health. The impact of hyperglycemia or its metabolites, advanced glycation end-products (AGEs), on glomerular endothelial cells (GECs) and their pathophysiologic mechanisms are not well explored. Our results reveal that AGEs increased the expression and secretion of the KIT ligand (KITLG) in GECs. Both AGEs and KITLG promoted endothelial-to-mesenchymal transition (EndoMT) in GECs and further increased the permeability of GECs through the AKT/extracellular-signal-regulated kinase pathway. Inhibition of KITLG’s effects by imatinib prevented AGE-medicated EndoMT in GECs, supporting the belief that KITLG is a critical factor for GEC injury. We found higher KITLG levels in the GECs and urine of db/db mice compared with db/m mice, and urinary KITLG levels were positively correlated with the urinary albumin-to-creatinine ratio (ACR). Furthermore, type 2 diabetic patients had higher urinary KITLG levels than normal individuals, as well as urinary KITLG levels that were positively correlated with urinary ACR and negatively correlated with the estimated glomerular filtration rate. KITLG plays a pathogenic role in GEC injury in DN and might act as a biomarker of DN progression. |
| first_indexed | 2024-03-09T21:38:45Z |
| format | Article |
| id | doaj.art-ef9792edfabc4d3d8a7c2e4899734056 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:38:45Z |
| publishDate | 2022-10-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ef9792edfabc4d3d8a7c2e48997340562023-11-23T20:38:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123191172310.3390/ijms231911723KITLG Promotes Glomerular Endothelial Cell Injury in Diabetic Nephropathy by an Autocrine EffectJiun-Chi Huang0Szu-Chia Chen1Wei-An Chang2Wei-Wen Hung3Ping-Hsun Wu4Ling-Yu Wu5Jer-Ming Chang6Ya-Ling Hsu7Yi-Chun Tsai8Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung 812, TaiwanDepartment of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung 812, TaiwanDivision of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, TaiwanDivision of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, TaiwanSchool of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanGraduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanSchool of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanDrug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807, TaiwanSchool of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanDiabetic nephropathy (DN) is an increasing threat to human health. The impact of hyperglycemia or its metabolites, advanced glycation end-products (AGEs), on glomerular endothelial cells (GECs) and their pathophysiologic mechanisms are not well explored. Our results reveal that AGEs increased the expression and secretion of the KIT ligand (KITLG) in GECs. Both AGEs and KITLG promoted endothelial-to-mesenchymal transition (EndoMT) in GECs and further increased the permeability of GECs through the AKT/extracellular-signal-regulated kinase pathway. Inhibition of KITLG’s effects by imatinib prevented AGE-medicated EndoMT in GECs, supporting the belief that KITLG is a critical factor for GEC injury. We found higher KITLG levels in the GECs and urine of db/db mice compared with db/m mice, and urinary KITLG levels were positively correlated with the urinary albumin-to-creatinine ratio (ACR). Furthermore, type 2 diabetic patients had higher urinary KITLG levels than normal individuals, as well as urinary KITLG levels that were positively correlated with urinary ACR and negatively correlated with the estimated glomerular filtration rate. KITLG plays a pathogenic role in GEC injury in DN and might act as a biomarker of DN progression.https://www.mdpi.com/1422-0067/23/19/11723KITLGadvanced glycation end-productsendothelial–to–mesenchymal transitionglomerular endothelial celldiabetic nephropathybiomarker |
| spellingShingle | Jiun-Chi Huang Szu-Chia Chen Wei-An Chang Wei-Wen Hung Ping-Hsun Wu Ling-Yu Wu Jer-Ming Chang Ya-Ling Hsu Yi-Chun Tsai KITLG Promotes Glomerular Endothelial Cell Injury in Diabetic Nephropathy by an Autocrine Effect International Journal of Molecular Sciences KITLG advanced glycation end-products endothelial–to–mesenchymal transition glomerular endothelial cell diabetic nephropathy biomarker |
| title | KITLG Promotes Glomerular Endothelial Cell Injury in Diabetic Nephropathy by an Autocrine Effect |
| title_full | KITLG Promotes Glomerular Endothelial Cell Injury in Diabetic Nephropathy by an Autocrine Effect |
| title_fullStr | KITLG Promotes Glomerular Endothelial Cell Injury in Diabetic Nephropathy by an Autocrine Effect |
| title_full_unstemmed | KITLG Promotes Glomerular Endothelial Cell Injury in Diabetic Nephropathy by an Autocrine Effect |
| title_short | KITLG Promotes Glomerular Endothelial Cell Injury in Diabetic Nephropathy by an Autocrine Effect |
| title_sort | kitlg promotes glomerular endothelial cell injury in diabetic nephropathy by an autocrine effect |
| topic | KITLG advanced glycation end-products endothelial–to–mesenchymal transition glomerular endothelial cell diabetic nephropathy biomarker |
| url | https://www.mdpi.com/1422-0067/23/19/11723 |
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