PMID- 26363223
OWN - NLM
STAT- MEDLINE
DCOM- 20161005
LR  - 20161230
IS  - 1872-8057 (Electronic)
IS  - 0303-7207 (Linking)
VI  - 417
DP  - 2015 Dec 5
TI  - Inhibition of c-Src/p38 MAPK pathway ameliorates renal tubular epithelial cells 
      apoptosis in db/db mice.
PG  - 27-35
LID - S0303-7207(15)30074-5 [pii]
LID - 10.1016/j.mce.2015.09.008 [doi]
AB  - Renal tubular epithelial cells (RTEC) apoptosis, which plays a key role in the 
      pathogenesis and progression of diabetic nephropathy (DN), is believed to be 
      contributive to the hyperglycemia-induced kidney failure, though the exact 
      mechanisms remain elusive. In this study, we investigated how inhibition of 
      c-Src/p38 MAPK pathway would affect RTEC apoptosis. The c-Src inhibitor PP2 i.p. 
      administered every other day for 8 weeks to diabetic db/db mice significantly 
      reduced their kidney weights, daily urinary volumes, blood glucose, blood urea 
      nitrogen, serum creatinine, triglyceride and urine albumin excretion, whereas 
      deactivation of c-Src and p38 MAPK were also observed, along with decreases in 
      both Bax/Bcl-2 ratio and cleaved caspase-3 level in the kidneys. In vitro, 
      exposure of HK-2 cells (a human RTEC line), to high glucose (HG) promoted 
      phosphorylation of c-Src and p38 MAPK, and subsequently, as revealed by western 
      blotting, TUNEL assay and flow cytometry, increased cell death, which can be 
      inhibited by PP2. Especially, a specific p38 MAPK inhibitor, SB203580, that both 
      attenuated HG-induced c-Src activation and abrogated the expression of PPARgamma and 
      CHOP, also reduced apoptosis. Taken together, PP2 inhibits c-Src and therefore 
      reduces apoptosis in RTEC, which at least in part, is due to suppressed p38 MAPK 
      activation in diabetic kidney.
CI  - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved.
FAU - Wu, Haijiang
AU  - Wu H
AD  - Department of Pathology, Hebei Medical University, Shijiazhuang, China; Key 
      Laboratory of Kidney Diseases of Hebei Province, Shijiazhufang, China.
FAU - Shi, Yonghong
AU  - Shi Y
AD  - Department of Pathology, Hebei Medical University, Shijiazhuang, China; Key 
      Laboratory of Kidney Diseases of Hebei Province, Shijiazhufang, China.
FAU - Deng, Xinna
AU  - Deng X
AD  - Department of Oncology & Immunotherapy, Hebei General Hospital, Shijiazhuang, 
      China.
FAU - Su, Ye
AU  - Su Y
AD  - Mathew Mailing Centre for Translational Transplantation Studies, Lawson Health 
      Research Institute, London Health Sciences Centre, Department of Medicine, and 
      Pathology, University of Western Ontario, London, Ontario, Canada.
FAU - Du, Chunyang
AU  - Du C
AD  - Department of Pathology, Hebei Medical University, Shijiazhuang, China; Key 
      Laboratory of Kidney Diseases of Hebei Province, Shijiazhufang, China.
FAU - Wei, Jinying
AU  - Wei J
AD  - Department of Pathology, Hebei Medical University, Shijiazhuang, China; Key 
      Laboratory of Kidney Diseases of Hebei Province, Shijiazhufang, China.
FAU - Ren, Yunzhuo
AU  - Ren Y
AD  - Department of Pathology, Hebei Medical University, Shijiazhuang, China; Key 
      Laboratory of Kidney Diseases of Hebei Province, Shijiazhufang, China.
FAU - Wu, Ming
AU  - Wu M
AD  - Department of Pathology, Hebei Medical University, Shijiazhuang, China; Key 
      Laboratory of Kidney Diseases of Hebei Province, Shijiazhufang, China.
FAU - Hou, Yanjuan
AU  - Hou Y
AD  - Department of Pathology, Hebei Medical University, Shijiazhuang, China; Key 
      Laboratory of Kidney Diseases of Hebei Province, Shijiazhufang, China.
FAU - Duan, Huijun
AU  - Duan H
AD  - Department of Pathology, Hebei Medical University, Shijiazhuang, China; Key 
      Laboratory of Kidney Diseases of Hebei Province, Shijiazhufang, China. Electronic 
      address: duanhuijun999@163.com.
LA  - eng
PT  - Journal Article
DEP - 20150910
PL  - Ireland
TA  - Mol Cell Endocrinol
JT  - Molecular and cellular endocrinology
JID - 7500844
RN  - 0 (AG 1879)
RN  - 0 (Pyrimidines)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Cell Line
MH  - Diabetic Nephropathies/drug therapy/*metabolism
MH  - Disease Models, Animal
MH  - Drug Administration Schedule
MH  - Epithelial Cells
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Kidney Tubules/*cytology/drug effects/metabolism
MH  - MAP Kinase Signaling System/*drug effects
MH  - Male
MH  - Mice
MH  - Pyrimidines/*administration & dosage/pharmacology
OTO - NOTNLM
OT  - Apoptosis
OT  - Diabetic nephropathy
OT  - c-Src
OT  - db/db mice
OT  - p38 MAPK
EDAT- 2015/09/13 06:00
MHDA- 2016/10/07 06:00
CRDT- 2015/09/13 06:00
PHST- 2015/05/19 00:00 [received]
PHST- 2015/08/05 00:00 [revised]
PHST- 2015/09/08 00:00 [accepted]
PHST- 2015/09/13 06:00 [entrez]
PHST- 2015/09/13 06:00 [pubmed]
PHST- 2016/10/07 06:00 [medline]
AID - S0303-7207(15)30074-5 [pii]
AID - 10.1016/j.mce.2015.09.008 [doi]
PST - ppublish
SO  - Mol Cell Endocrinol. 2015 Dec 5;417:27-35. doi: 10.1016/j.mce.2015.09.008. Epub 
      2015 Sep 10.