title: Reduced Krüppel-like factor 2 expression may aggravate the endothelial injury of diabetic nephropathy.
abstract: Krüppel-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.
authors.affiliation: 1] Department of Medicine/Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, USA [2] Department of Nephrology, Hang Zhou Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Zhejiang, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhong
authors.affiliation: 1] Department of Medicine/Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, USA [2] Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Habing
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Medicine/Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Chengguo
authors.initials: C
authors.lastname: Wei
authors.affiliation: Department of Medicine/Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Weijia
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Medicine/Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Zhengzhe
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Medicine, Case Cardiovascular Research Institute, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Mukesh K
authors.initials: MK
authors.lastname: Jain
authors.affiliation: Department of Medicine/Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Peter Y
authors.initials: PY
authors.lastname: Chuang
authors.affiliation: Department of Nephrology, Hang Zhou Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Zhejiang, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Nephrology, Hang Zhou Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Zhejiang, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Division of Nephrology, Department of Medicine, Stony Brook University, Stony Brook, New York, USA.
authors.forename: Sandeep K
authors.initials: SK
authors.lastname: Mallipattu
authors.affiliation: 1] Department of Medicine/Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, USA [2] Renal Section, James J Peters VAMC, Bronx, New York, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: He
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D051741:Kruppel-Like Transcription Factors / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D050199:Podocytes / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
chemical_list: D007328:Insulin; C498314:Klf2 protein, mouse; C543921:Klf2 protein, rat; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; D005947:Glucose