PMID- 34894065
OWN - NLM
STAT- MEDLINE
DCOM- 20220202
LR  - 20220202
IS  - 1522-7278 (Electronic)
IS  - 1520-4081 (Linking)
VI  - 37
IP  - 3
DP  - 2022 Mar
TI  - beta-Amyrin ameliorates diabetic nephropathy in mice and regulates the 
      miR-181b-5p/HMGB2 axis in high glucose-stimulated HK-2 cells.
PG  - 637-649
LID - 10.1002/tox.23431 [doi]
AB  - Diabetic nephropathy (DN) is a diabetic complication that can cause renal 
      failure. beta-amyrin has been identified to possess anti-diabetic property. This 
      study was designed to evaluate the potential role of beta-amyrin in DN and its 
      underlying mechanism. Streptozotocin-induced diabetic mice were used as the in 
      vivo model, and high glucose (HG)-stimulated human proximal tubular HK-2 cells 
      were utilized as the in vitro model. Renal histological changes in mice were 
      assessed by hematoxylin-eosin and periodic acid-Schiff staining. HK-2 cell 
      viability and apoptosis were detected by Cell Counting Kit-8 assay and flow 
      cytometry analysis, respectively. beta-amyrin was found to ameliorate kidney injury 
      in DN mice and suppressed inflammatory response as well as apoptosis of 
      HG-stimulated HK-2 cells. miR-181-5p expression in murine renal tissues and HK-2 
      cells was detected by in situ hybridization (ISH) and fluorescence in situ 
      hybridization (FISH). MiR-181b-5p, a previously identified target for diabetic 
      kidney disease, was downregulated in renal tissues and HG stimulated HK-2 cells, 
      and beta-amyrin induced the upregulation of miR-181b-5p. Binding relationship 
      between miR-181b-5p and high mobility group box 2 (HMGB2) was confirmed by 
      luciferase reporter assay. MiR-181b-5p bound to 3' untranslated region of HMGB2 
      to suppress its expression. As shown by immunohistochemical staining and 
      immunofluorescence staining, HMGB2 was upregulated in the in vivo and in vitro 
      models of DN, and beta-amyrin induced the downregulation of HMGB2. Moreover, HMGB2 
      overexpression neutralized the suppressive effects of miR-181b-5p elevation on 
      the inflammatory response and apoptosis of HG-treated HK-2 cells. Overall, 
      beta-amyrin ameliorates DN in mice and suppresses inflammatory response and 
      apoptosis of HG-stimulated HK-2 cells via the miR-181b-5p/HMGB2 axis.
CI  - (c) 2021 Wiley Periodicals LLC.
FAU - Xu, Wenhua
AU  - Xu W
AUID- ORCID: 0000-0001-5552-0183
AD  - Preventive Treatment Center, Shenzhen Hospital of Integrated Traditional Chinese 
      and Western Medicine, Shenzhen, Guangdong, China.
FAU - Zhang, Hongwu
AU  - Zhang H
AD  - Department of Endocrinology, Shenzhen Hospital of Integrated Traditional Chinese 
      and Western Medicine, Shenzhen, Guangdong, China.
FAU - Zhang, Qinfeng
AU  - Zhang Q
AD  - Department of Endocrinology, Shenzhen Hospital of Integrated Traditional Chinese 
      and Western Medicine, Shenzhen, Guangdong, China.
FAU - Xu, Jialan
AU  - Xu J
AD  - Preventive Treatment Center, Shenzhen Hospital of Integrated Traditional Chinese 
      and Western Medicine, Shenzhen, Guangdong, China.
LA  - eng
GR  - The Fourth Batch of National Chinese Medicine (Clinical, Basic) Outstanding 
      Talents Research and Training Projects by National Administration of Traditional 
      Chinese Medicine (No. Traditional Chinese Medicine Education and Development 
      [2017] 24)./
PT  - Journal Article
DEP - 20211211
PL  - United States
TA  - Environ Toxicol
JT  - Environmental toxicology
JID - 100885357
RN  - 0 (HMGB2 Protein)
RN  - 0 (MicroRNAs)
RN  - 6SMK8R7TGJ (Oleanolic Acid)
RN  - IY9XDZ35W2 (Glucose)
RN  - KM8353IPSO (beta-amyrin)
SB  - IM
MH  - Animals
MH  - *Diabetes Mellitus, Experimental
MH  - *Diabetic Nephropathies/genetics
MH  - Glucose
MH  - HMGB2 Protein
MH  - In Situ Hybridization, Fluorescence
MH  - Mice
MH  - *MicroRNAs/genetics
MH  - Oleanolic Acid/analogs & derivatives
OTO - NOTNLM
OT  - DN
OT  - HMGB2
OT  - apoptosis
OT  - inflammatory response
OT  - miR-181b-5p
OT  - beta-amyrin
EDAT- 2021/12/12 06:00
MHDA- 2022/02/03 06:00
CRDT- 2021/12/11 06:25
PHST- 2021/11/22 00:00 [revised]
PHST- 2021/08/09 00:00 [received]
PHST- 2021/11/27 00:00 [accepted]
PHST- 2021/12/12 06:00 [pubmed]
PHST- 2022/02/03 06:00 [medline]
PHST- 2021/12/11 06:25 [entrez]
AID - 10.1002/tox.23431 [doi]
PST - ppublish
SO  - Environ Toxicol. 2022 Mar;37(3):637-649. doi: 10.1002/tox.23431. Epub 2021 Dec 
      11.