PMID- 36004694 OWN - NLM STAT- MEDLINE DCOM- 20220826 LR - 20220919 IS - 1045-4403 (Print) IS - 1045-4403 (Linking) VI - 32 IP - 7 DP - 2022 TI - Kruppel Like Factor 5 Enhances High Glucose-Induced Renal Tubular Epithelial Cell Transdifferentiation in Diabetic Nephropathy. PG - 35-45 LID - 10.1615/CritRevEukaryotGeneExpr.2022043565 [doi] AB - Background - Diabetic nephropathy (DN) is a principal reason for kidney disease worldwide. High glucose (HG) is a major factor for DN. Kruppel like factor 5 (KLF5) participates in DN development. In the present study, we aim to elaborate the role of KLF5 in HG-induced renal tubular epithelial cell (RTEC) transdifferentiation in DN. Methods - RTECs (HK-2 cells) were treated with HG and were transfected with si-KLF5 or oe-HMGB1. Afterwards, expression of KLF5 and HMGB1 was detected, HK cell viability was determined, and levels of alpha-smooth muscle actin (alpha-SMA), E-cadherin, vimentin, and transforming growth factor beta 1 (TGF-beta1) were assessed. Additionally, the binding relation between KLF5 and HMGB1 was analyzed. Results - In HK-2 cells with HG treatment, expression of KLF5 and HMGB1 was upregulated; levels of alpha-SMA, vimentin, and TGF-beta1 were increased; and E-cadherin level was decreased. Moreover, KLF5 silencing resulted in down-regulated levels of alpha-SMA, vimentin, and TGF-beta1 but upregulated level of E-cadherin. On the other hand, KLF5 could bind to the HMGB1 promoter and activate HMGB1 transcription. HMGB1 overexpression partially counteracted the inhibitive effect of KLF5 silencing on HG-induced HK-2 transdifferentiation. Conclusion - HG induced overexpressed KLF5 in RTECs, and as a transcription factor, KLF5 could bind to the HMGB1 promoter, thereby promoting HMGB1 transcription and RTEC transdifferentiation. FAU - Zou, Hongchang AU - Zou H AD - Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China. FAU - Zhu, Shuying AU - Zhu S AD - Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China. FAU - Chen, Yanxia AU - Chen Y AD - Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China. FAU - Cai, Ni AU - Cai N AD - Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China. FAU - Xu, Chengyun AU - Xu C AD - Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China. FAU - Tu, Weiping AU - Tu W AD - Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China. FAU - Qin, Xiaohua AU - Qin X AD - Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Crit Rev Eukaryot Gene Expr JT - Critical reviews in eukaryotic gene expression JID - 9007261 RN - 0 (Cadherins) RN - 0 (HMGB1 Protein) RN - 0 (Kruppel-Like Transcription Factors) RN - 0 (Transcription Factors) RN - 0 (Transforming Growth Factor beta1) RN - 0 (Vimentin) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Cadherins/genetics/metabolism MH - Cell Transdifferentiation/genetics MH - *Diabetes Mellitus MH - *Diabetic Nephropathies/genetics/metabolism MH - Epithelial Cells/metabolism MH - Glucose/metabolism/pharmacology MH - *HMGB1 Protein/metabolism/pharmacology MH - Humans MH - Kruppel-Like Transcription Factors/genetics/metabolism MH - Transcription Factors/metabolism MH - Transforming Growth Factor beta1/genetics/metabolism/pharmacology MH - Vimentin/genetics/metabolism/pharmacology EDAT- 2022/08/26 06:00 MHDA- 2022/08/27 06:00 CRDT- 2022/08/25 05:43 PHST- 2022/08/25 05:43 [entrez] PHST- 2022/08/26 06:00 [pubmed] PHST- 2022/08/27 06:00 [medline] AID - 0a7b625a5f38a24a,4d002c264b8639dd [pii] AID - 10.1615/CritRevEukaryotGeneExpr.2022043565 [doi] PST - ppublish SO - Crit Rev Eukaryot Gene Expr. 2022;32(7):35-45. doi: 10.1615/CritRevEukaryotGeneExpr.2022043565.