Calmodulin-dependent protein kinase II activation promotes kidney mesangial expansion in streptozotocin-induced diabetic mice
Calcium-calmodulin-dependent protein kinase II (CaMKII) is upregulated in diabetes mellitus (DM), leading to the overproduction of collagen in the myocardium. We hypothesized that CaMKII plays a role in the development of diabetic nephropathy (DN). Streptozotocin (STZ) injection into FVB wild-type m...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844022029413 |
| _version_ | 1798014442009526272 |
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| author | Alexei V. Mikhailov Yixi Liu Heng-Jie Cheng Jen-Jar Lin Che Ping Cheng |
| author_facet | Alexei V. Mikhailov Yixi Liu Heng-Jie Cheng Jen-Jar Lin Che Ping Cheng |
| author_sort | Alexei V. Mikhailov |
| collection | DOAJ |
| description | Calcium-calmodulin-dependent protein kinase II (CaMKII) is upregulated in diabetes mellitus (DM), leading to the overproduction of collagen in the myocardium. We hypothesized that CaMKII plays a role in the development of diabetic nephropathy (DN). Streptozotocin (STZ) injection into FVB wild-type mice led to mild mesangial matrix expansion, reproducing an essential feature of early human DN. Mesangial matrix measurements were performed on trichrome-stained paraffin sections using a trainable segmentation method based on WEKA (Waikato Environment for Knowledge Analysis) Image J-Fiji plugin (TWS plugin), and the electron micrographs of the whole glomeruli stitched from individual 4800x partial glomerular images. Both methods demonstrated that the statistically significant mesangial matrix expansion seen in the diabetic mice was prevented by chronic pretreatment with KN-93, a small molecule CaMKII inhibitor. This study indicates a role for CaMKII in the development of mesangial alterations in diabetes and suggests a possible new therapeutic target. |
| first_indexed | 2024-04-11T15:18:20Z |
| format | Article |
| id | doaj.art-adb3bb76858a4c08ac7bc8430969803e |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-11T15:18:20Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-adb3bb76858a4c08ac7bc8430969803e2022-12-22T04:16:26ZengElsevierHeliyon2405-84402022-11-01811e11653Calmodulin-dependent protein kinase II activation promotes kidney mesangial expansion in streptozotocin-induced diabetic miceAlexei V. Mikhailov0Yixi Liu1Heng-Jie Cheng2Jen-Jar Lin3Che Ping Cheng4Department of Pathology, Atrium Health Wake Forest School of Medicine, Winston-Salem, NC, USA; Corresponding author.Cardiovascular Medicine, Atrium Health Wake Forest School of Medicine, Winston-Salem, NC, USACardiovascular Medicine, Atrium Health Wake Forest School of Medicine, Winston-Salem, NC, USADepartment of Pediatrics, Atrium Health Wake Forest School of Medicine, Winston-Salem, NC, USACardiovascular Medicine, Atrium Health Wake Forest School of Medicine, Winston-Salem, NC, USACalcium-calmodulin-dependent protein kinase II (CaMKII) is upregulated in diabetes mellitus (DM), leading to the overproduction of collagen in the myocardium. We hypothesized that CaMKII plays a role in the development of diabetic nephropathy (DN). Streptozotocin (STZ) injection into FVB wild-type mice led to mild mesangial matrix expansion, reproducing an essential feature of early human DN. Mesangial matrix measurements were performed on trichrome-stained paraffin sections using a trainable segmentation method based on WEKA (Waikato Environment for Knowledge Analysis) Image J-Fiji plugin (TWS plugin), and the electron micrographs of the whole glomeruli stitched from individual 4800x partial glomerular images. Both methods demonstrated that the statistically significant mesangial matrix expansion seen in the diabetic mice was prevented by chronic pretreatment with KN-93, a small molecule CaMKII inhibitor. This study indicates a role for CaMKII in the development of mesangial alterations in diabetes and suggests a possible new therapeutic target.http://www.sciencedirect.com/science/article/pii/S2405844022029413Diabetic nephropathyStreptozotocinCalmodulin-dependent protein kinase IIKN-93MesangiumWEKA Image J plugin |
| spellingShingle | Alexei V. Mikhailov Yixi Liu Heng-Jie Cheng Jen-Jar Lin Che Ping Cheng Calmodulin-dependent protein kinase II activation promotes kidney mesangial expansion in streptozotocin-induced diabetic mice Heliyon Diabetic nephropathy Streptozotocin Calmodulin-dependent protein kinase II KN-93 Mesangium WEKA Image J plugin |
| title | Calmodulin-dependent protein kinase II activation promotes kidney mesangial expansion in streptozotocin-induced diabetic mice |
| title_full | Calmodulin-dependent protein kinase II activation promotes kidney mesangial expansion in streptozotocin-induced diabetic mice |
| title_fullStr | Calmodulin-dependent protein kinase II activation promotes kidney mesangial expansion in streptozotocin-induced diabetic mice |
| title_full_unstemmed | Calmodulin-dependent protein kinase II activation promotes kidney mesangial expansion in streptozotocin-induced diabetic mice |
| title_short | Calmodulin-dependent protein kinase II activation promotes kidney mesangial expansion in streptozotocin-induced diabetic mice |
| title_sort | calmodulin dependent protein kinase ii activation promotes kidney mesangial expansion in streptozotocin induced diabetic mice |
| topic | Diabetic nephropathy Streptozotocin Calmodulin-dependent protein kinase II KN-93 Mesangium WEKA Image J plugin |
| url | http://www.sciencedirect.com/science/article/pii/S2405844022029413 |
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