PMID- 33125105
OWN - NLM
STAT- MEDLINE
DCOM- 20210708
LR  - 20210708
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 46
IP  - 6
DP  - 2020 Dec
TI  - MicroRNA‑199a‑3p suppresses high glucose‑induced apoptosis and inflammation by 
      regulating the IKKbeta/NF‑kappaB signaling pathway in renal tubular epithelial cells.
PG  - 2161-2171
LID - 10.3892/ijmm.2020.4751 [doi]
AB  - Renal tubular epithelial cells (RTEC) injury induced by hyperglycemia is 
      considered a major contributor to the pathogenesis of diabetic nephropathy (DN). 
      However, few studies have focused on the role of microRNAs (miRNAs/miRs) in RTEC 
      injury. Therefore, the present study aimed to investigate the role and mechanisms 
      of miRNAs in RTEC injury. In the study, miRNAs expression profiles were 
      determined via microarray assay in the peripheral blood samples of patients with 
      DN. High glucose (HG)‑induced injury in HK‑2 cells was used as a cell model to 
      examine the potential role of miR‑199a‑3p in DN. The expression of miR‑199a‑3p 
      was validated using reverse transcription‑quantitative PCR. The expressions of 
      TNF‑alpha, IL‑1beta and IL‑6, were detected via ELISA. The protein levels of 
      apoptosis‑related proteins were determined using western blotting. Cell apoptosis 
      and caspase 3 activity were evaluated via flow cytometry analysis and caspase 3 
      activity assay, respectively. Luciferase reporter assay was used to confirm the 
      interaction between miR‑199a‑3p and IKKbeta. miR‑199a‑3p was found to be 
      significantly downregulated in the peripheral blood samples, and there was a 
      negative correlation between miR‑199a‑3p expression and proteinuria in patients 
      with DN. It was identified that miR‑199a‑3p expression was time‑dependently 
      decreased in the HG‑induced cell damage model. Moreover, miR‑199a‑3p 
      overexpression significantly improved HG‑induced cell injury, as evidenced by the 
      decrease in cell apoptosis and inflammation. Subsequent analyses demonstrated 
      that miR‑199a‑3p directly targeted IKKbeta, whose expression was increased, and 
      negatively correlated with miR‑199a‑3p expression in patients with DN. The 
      protective effects of miR‑199a‑3p overexpression on HG‑treated HK‑2 cells were 
      partially reversed by IKKbeta overexpression. In addition, activation of the NF‑kappaB 
      pathway by HG was blocked by miR‑199a‑3p mimics transfection in HK‑2 cells. 
      Collectively, the present findings indicated that miR‑199a‑3p protected HK‑2 
      cells against HG‑induced injury via inactivation of the IKKbeta/NF‑kappaB pathway, 
      suggesting enhanced expression of miR‑199a‑3p as a potential therapeutic strategy 
      for patients with DN.
FAU - Zhang, Ruimin
AU  - Zhang R
AD  - Department of Nephrology, Huaihe Hospital of Henan University, Kaifeng, Henan 
      475000, P.R. China.
FAU - Qin, Linfang
AU  - Qin L
AD  - Department of Nephrology, Huaihe Hospital of Henan University, Kaifeng, Henan 
      475000, P.R. China.
FAU - Shi, Jun
AU  - Shi J
AD  - Department of Nephrology, Huaihe Hospital of Henan University, Kaifeng, Henan 
      475000, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20201012
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (MicroRNAs)
RN  - 0 (NF-kappa B)
RN  - 0 (mirn199 microRNA, human)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adult
MH  - Apoptosis/drug effects/*genetics
MH  - Base Sequence
MH  - Diabetic Nephropathies/genetics/pathology
MH  - Down-Regulation/drug effects
MH  - Epithelial Cells/drug effects/*metabolism
MH  - Female
MH  - Glucose/*toxicity
MH  - Humans
MH  - I-kappa B Kinase/*metabolism
MH  - Inflammation/*genetics/pathology
MH  - Kidney Tubules/*pathology
MH  - Male
MH  - MicroRNAs/genetics/*metabolism
MH  - Middle Aged
MH  - NF-kappa B/*metabolism
MH  - *Signal Transduction/drug effects
MH  - Young Adult
PMC - PMC7595662
EDAT- 2020/10/31 06:00
MHDA- 2021/07/09 06:00
PMCR- 2020/10/12
CRDT- 2020/10/30 12:09
PHST- 2020/04/03 00:00 [received]
PHST- 2020/09/11 00:00 [accepted]
PHST- 2020/10/31 06:00 [pubmed]
PHST- 2021/07/09 06:00 [medline]
PHST- 2020/10/30 12:09 [entrez]
PHST- 2020/10/12 00:00 [pmc-release]
AID - ijmm-46-06-2161 [pii]
AID - 10.3892/ijmm.2020.4751 [doi]
PST - ppublish
SO  - Int J Mol Med. 2020 Dec;46(6):2161-2171. doi: 10.3892/ijmm.2020.4751. Epub 2020 
      Oct 12.