PMID- 35129424
OWN - NLM
STAT- MEDLINE
DCOM- 20220408
LR  - 20220711
IS  - 2165-5987 (Electronic)
IS  - 2165-5979 (Print)
IS  - 2165-5979 (Linking)
VI  - 13
IP  - 2
DP  - 2022 Feb
TI  - Identification of circular RNAs and functional competing endogenous RNA networks 
      in human proximal tubular epithelial cells treated with sodium-glucose 
      cotransporter 2 inhibitor dapagliflozin in diabetic kidney disease.
PG  - 3911-3929
LID - 10.1080/21655979.2022.2031391 [doi]
AB  - Diabetic kidney disease (DKD) is a serious diabetes complication. Sodium-glucose 
      cotransporter 2 inhibitors (SGLT2i) are novel anti-diabetes drugs that confer 
      clinical renal protection. However, the molecular mechanisms involved remain 
      unclear. Here, human proximal tubular epithelial cells (PTECs) were treated with 
      normal glucose, high glucose, and anti-diabetes agents, including SGLT2i 
      (dapagliflozin), metformin, and dipeptidyl peptidase-4 inhibitor (DPP-4i, 
      vildagliptin) and microarray analysis was performed. Firstly, a total of 2,710 
      differentially expressed circular RNAs (circRNAs) were identified. Secondly, 
      network pharmacology and transcriptomics analyses showed that the effects of 
      dapagliflozin on PTECs primarily involved lipid metabolism, Rap1, and MAPK 
      signaling pathways. Metformin mainly affected the AMPK and FOXO signaling 
      pathways, whereas vildagliptin affected insulin secretion and the HIF-1 signaling 
      pathway. Furthermore, circRNA-miRNA-mRNA networks, real-time reverse 
      transcription-polymerase chain reaction (RT-PCR), and fluorescence in situ 
      hybridization (FISH) assay revealed that the expression of hsa_circRNA_012448 was 
      increased in PTECs treated with high glucose, whereas its expression was reversed 
      by dapagliflozin. Finally, the hsa_circRNA_012448-hsa-miR-29b-2-5p-GSK3beta pathway, 
      involved in the oxidative stress response, was identified as an important pathway 
      mediating the action of dapagliflozin against DKD. Overall, our study provides 
      novel insights into the molecular mechanisms underlying the effects of 
      dapagliflozin on DKD.
FAU - Song, Yi
AU  - Song Y
AD  - Department of Endocrinology and Metabolism, The First Affiliated Hospital of 
      Zhengzhou University, Zhengzhou, China.
AD  - Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
FAU - Guo, Feng
AU  - Guo F
AD  - Department of Endocrinology and Metabolism, The First Affiliated Hospital of 
      Zhengzhou University, Zhengzhou, China.
AD  - Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
FAU - Liu, Yifan
AU  - Liu Y
AD  - Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-sen 
      University, Guangzhou, China.
FAU - Huang, Fengjuan
AU  - Huang F
AD  - Department of Endocrinology and Metabolism, The First Affiliated Hospital of 
      Zhengzhou University, Zhengzhou, China.
FAU - Fan, Xunjie
AU  - Fan X
AD  - Department of Endocrinology and Metabolism, The First Affiliated Hospital of 
      Zhengzhou University, Zhengzhou, China.
AD  - Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
FAU - Zhao, Lin
AU  - Zhao L
AD  - Department of Endocrinology and Metabolism, The First Affiliated Hospital of 
      Zhengzhou University, Zhengzhou, China.
FAU - Qin, Guijun
AU  - Qin G
AD  - Department of Endocrinology and Metabolism, The First Affiliated Hospital of 
      Zhengzhou University, Zhengzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Bioengineered
JT  - Bioengineered
JID - 101581063
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Glucosides)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (MIRN29B1 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Circular)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - 1ULL0QJ8UC (dapagliflozin)
RN  - 9100L32L2N (Metformin)
RN  - 9NEZ333N27 (Sodium)
RN  - I6B4B2U96P (Vildagliptin)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Benzhydryl Compounds
MH  - *Diabetes Mellitus
MH  - *Diabetic Nephropathies/drug therapy/genetics/metabolism
MH  - Epithelial Cells/metabolism
MH  - Glucose/metabolism
MH  - Glucosides
MH  - Humans
MH  - Hypoglycemic Agents/pharmacology/therapeutic use
MH  - In Situ Hybridization, Fluorescence
MH  - *Metformin/therapeutic use
MH  - MicroRNAs
MH  - RNA, Circular/genetics
MH  - Sodium/therapeutic use
MH  - Sodium-Glucose Transporter 2 Inhibitors/*pharmacology
MH  - Vildagliptin/therapeutic use
PMC - PMC8973950
OTO - NOTNLM
OT  - Dapagliflozin
OT  - circRNA
OT  - competing endogenous RNAs
OT  - diabetic kidney disease
OT  - mRNA
OT  - proximal tubular epithelial cells
COIS- No potential conflict of interest was reported by the author(s).
EDAT- 2022/02/08 06:00
MHDA- 2022/04/09 06:00
PMCR- 2022/02/07
CRDT- 2022/02/07 12:13
PHST- 2022/02/07 12:13 [entrez]
PHST- 2022/02/08 06:00 [pubmed]
PHST- 2022/04/09 06:00 [medline]
PHST- 2022/02/07 00:00 [pmc-release]
AID - 2031391 [pii]
AID - 10.1080/21655979.2022.2031391 [doi]
PST - ppublish
SO  - Bioengineered. 2022 Feb;13(2):3911-3929. doi: 10.1080/21655979.2022.2031391.