Reduced Krüppel-like factor 2 expression may aggravate the endothelial injury of diabetic nephropathy
| Autor: | Mukesh K. Jain, Hongyu Chen, Chengguo Wei, John Cijiang He, Fang Zhong, Zhengzhe Li, Sandeep K. Mallipattu, Yongjun Wang, Weijia Zhang, Habing Chen, Peter Y. Chuang |
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| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
podocyte endothelium Endothelium medicine.medical_treatment Kidney Glomerulus Kruppel-Like Transcription Factors Article Diabetes Mellitus Experimental Diabetic nephropathy Mice Internal medicine Human Umbilical Vein Endothelial Cells medicine Animals Humans Insulin Diabetic Nephropathies RNA Messenger Mice Knockout biology Podocytes business.industry diabetic nephropathy Glomerular Hypertrophy medicine.disease Angiopoietin receptor Rats Endothelial stem cell Vascular endothelial growth factor A Glucose Endocrinology medicine.anatomical_structure Gene Expression Regulation Nephrology Gene Knockdown Techniques Knockout mouse biology.protein Endothelium Vascular business |
| Zdroj: | Kidney international |
| ISSN: | 0085-2538 |
| Popis: | Kruppel-like factor 2 (KLF2), a shear stress–inducible transcription factor, has endoprotective effects. In streptozotocin-induced diabetic rats, we found that glomerular Klf2 expression was reduced in comparison with nondiabetic rats. However, normalization of hyperglycemia by insulin treatment increased Klf2 expression to a level higher than that of nondiabetic rats. Consistent with this, we found that Klf2 expression was suppressed by high glucose but increased by insulin in cultured endothelial cells. To determine the role of KLF2 in streptozotocin-induced diabetic nephropathy, we used endothelial cell–specific Klf2 heterozygous knockout mice and found that diabetic knockout mice developed more kidney/glomerular hypertrophy and proteinuria than diabetic wild-type mice. Glomerular expression of Vegfa , Flk1 , and angiopoietin 2 increased, but expression of Flt1 , Tie2 , and angiopoietin 1 decreased, in diabetic knockout mice compared with diabetic wild-type mice. Glomerular expression of ZO-1, glycocalyx, and eNOS was also decreased in diabetic knockout compared with diabetic wild-type mice. These data suggest knockdown of Klf2 expression in the endothelial cells induced more endothelial cell injury. Interestingly, podocyte injury was also more prominent in diabetic knockout compared with diabetic wild-type mice, indicating a cross talk between these two cell types. Thus, KLF2 may play a role in glomerular endothelial cell injury in early diabetic nephropathy. |
| Databáze: | OpenAIRE |
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