AI Article Synopsis
- Calcium-calmodulin-dependent protein kinase II (CaMKII) is increased in diabetes, contributing to excess collagen in heart tissue, which may be linked to diabetic nephropathy (DN).
- In a study with mice induced with diabetes using streptozotocin, researchers observed early signs of DN, such as mesangial matrix expansion, a characteristic also found in humans.
- Treatment with KN-93, a CaMKII inhibitor, successfully prevented the mesangial matrix expansion in diabetic mice, highlighting CaMKII as a potential target for new diabetes therapies.
Article Abstract
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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9674542 | PMC |
| http://dx.doi.org/10.1016/j.heliyon.2022.e11653 | DOI Listing |
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