PMID- 30677774
OWN - NLM
STAT- MEDLINE
DCOM- 20191231
LR  - 20191231
IS  - 2235-3186 (Electronic)
IS  - 1660-8151 (Linking)
VI  - 142
IP  - 1
DP  - 2019
TI  - Roles of 12-Lipoxygenase and Its Interaction with Angiotensin II on p21 and p27 
      Expression in Diabetic Nephropathy.
PG  - 61-70
LID - 10.1159/000496440 [doi]
AB  - BACKGROUND: 12-Lipoxygenase (12-LO) and angiotensin II (Ang II) are involved in 
      the development of diabetic renal hypertrophy, in which cyclin-kinase inhibitors, 
      p21 and p27 play pivotal roles. Here, we study the effects of 12-LO and its 
      interaction with Ang II on glomerular p21 and p27 expression in diabetic 
      conditions. METHODS: Models used in the current study include glomerular 
      mesangial cells (MCs); and glomeruli from (1) type 2 diabetic db/db mice; (2) 
      type 2 diabetic rats induced by high-fat diet feeding followed by streptozotocin 
      injection; (3) 12-LO knockout (12-LOKO) mice; and (4) normal rats infused with 
      Ang II or 12(S)-hydroxyeicosatetraenoic acid (12[S]-HETE, arachidonic acid 
      metabolite of 12-LO). RESULTS: The protein expression levels of p21 and p27 were 
      increased in high glucose-stimulated MCs and in glomeruli isolated from db/db 
      mice. In type 2 diabetic rats, cinnamyl-3,4-dihydroxy-alpha-cynanocinnamate 
      (inhibitor of 12-LO) attenuated the increases in glomerular p21 and p27 protein 
      expression, while in normal rats, 12(S)-HETE injection increased glomerular p21 
      and p27 expression. 12(S)-HETE and Ang II were mutually stimulated in glomeruli. 
      Glomerular p21 and p27 expression were decreased in 12-LOKO mice compared to 
      levels in control mice, and Ang II stimulation increased the protein expression 
      of p27 in control but not 12-LOKO mice. Ang II stimulation had no effect on p21 
      protein expression in 12-LOKO mice. CONCLUSION: 12-LO is involved in diabetic 
      renal hypertrophy via the induction of p21 and p27 protein expression and 
      interacts with Ang II to induce p27 upregulation in diabetes. The current results 
      suggest a potential amplifying loop in the pathogenesis of diabetic nephropathy.
CI  - (c) 2019 S. Karger AG, Basel.
FAU - Zhang, Yuan-Yuan
AU  - Zhang YY
AD  - Department of Nephrology, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Wang, Wan-Ning
AU  - Wang WN
AD  - Department of Nephrology, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Su, Sen-Sen
AU  - Su SS
AD  - Department of Nephrology, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Chen, Bin
AU  - Chen B
AD  - Department of Nephrology, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Sun, Wei-Xia
AU  - Sun WX
AD  - Department of Nephrology, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Wu, Hao
AU  - Wu H
AD  - Department of Nephrology, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Cheng, Yan-Li
AU  - Cheng YL
AD  - Department of Nephrology, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Xu, Zhong-Gao
AU  - Xu ZG
AD  - Department of Nephrology, The First Hospital of Jilin University, Changchun, 
      China, renalxu@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190124
PL  - Switzerland
TA  - Nephron
JT  - Nephron
JID - 0331777
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 11128-99-7 (Angiotensin II)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
RN  - EC 1.13.11.31 (Arachidonate 12-Lipoxygenase)
SB  - IM
MH  - Angiotensin II/*metabolism
MH  - Animals
MH  - Arachidonate 12-Lipoxygenase/*metabolism
MH  - Cyclin-Dependent Kinase Inhibitor p21/*metabolism
MH  - Cyclin-Dependent Kinase Inhibitor p27/*metabolism
MH  - Diabetic Nephropathies/*metabolism
MH  - Kidney Glomerulus/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Rats
MH  - Rats, Sprague-Dawley
OTO - NOTNLM
OT  - 12-Lipoxygenase
OT  - Angiotensin II
OT  - Diabetic nephropathy
OT  - p21
OT  - p27
EDAT- 2019/01/25 06:00
MHDA- 2020/01/01 06:00
CRDT- 2019/01/25 06:00
PHST- 2018/01/07 00:00 [received]
PHST- 2018/12/21 00:00 [accepted]
PHST- 2019/01/25 06:00 [pubmed]
PHST- 2020/01/01 06:00 [medline]
PHST- 2019/01/25 06:00 [entrez]
AID - 000496440 [pii]
AID - 10.1159/000496440 [doi]
PST - ppublish
SO  - Nephron. 2019;142(1):61-70. doi: 10.1159/000496440. Epub 2019 Jan 24.