PMID- 22236035
OWN - NLM
STAT- MEDLINE
DCOM- 20130708
LR  - 20230829
IS  - 1538-7836 (Electronic)
IS  - 1538-7836 (Linking)
VI  - 10
IP  - 3
DP  - 2012 Mar
TI  - Exogenous activated protein C inhibits the progression of diabetic nephropathy.
PG  - 337-46
LID - 10.1111/j.1538-7836.2012.04621.x [doi]
AB  - BACKGROUND: Activated protein C (APC) can regulate immune and inflammatory 
      responses and apoptosis. Protein C transgenic mice develop less diabetic 
      nephropathy but whether exogenous administration of APC suppresses established 
      diabetic nephropathy is unknown. OBJECTIVES: We investigated the therapeutic 
      potential of APC in mice with streptozotocin-induced diabetic nephropathy. 
      METHODS: Diabetes was induced in unilaterally nephrectomized C57/Bl6 mice using 
      intraperitoneal (i.p.) injection of streptozotocin. Four weeks later, the mice 
      were treated with i.p. exogenous APC every other day for 1 month. RESULTS: 
      APC-treated mice had a significantly improved blood nitrogen urea-to-creatinine 
      ratio, urine total protein to creatinine ratio and proteinuria, and had 
      significantly less renal fibrosis as measured by the levels of collagen and 
      hydroxyproline. The renal tissue concentration of monocyte chemoattractant 
      protein-1 (MCP-1), vascular endothelial growth factor (VEGF) and the RNA 
      expression of platelet-derived growth factor (PDGF), transforming growth 
      factor-beta1 and connective tissue growth factor (CTGF) were significantly lower in 
      APC-treated mice than in untreated animals. The percentage of apoptotic cells was 
      reduced and the expression of podocin, nephrin and WT-1 in the glomeruli was 
      significantly improved in mice treated with APC compared with untreated mice. The 
      levels of coagulation markers were not affected by APC treatment. CONCLUSION: 
      Exogenous APC improves renal function and mitigates pathological changes in mice 
      with diabetic nephropathy by suppressing the expression of fibrogenic cytokines, 
      growth factors and apoptosis, suggesting its potential usefulness for the therapy 
      of this disease.
CI  - (c) 2012 International Society on Thrombosis and Haemostasis.
FAU - Gil-Bernabe, P
AU  - Gil-Bernabe P
AD  - Department of Diabetes and Metabolism, Mie University Graduate School of 
      Medicine, Tsu City, Mie Prefecture, Japan.
FAU - D'Alessandro-Gabazza, C N
AU  - D'Alessandro-Gabazza CN
FAU - Toda, M
AU  - Toda M
FAU - Boveda Ruiz, D
AU  - Boveda Ruiz D
FAU - Miyake, Y
AU  - Miyake Y
FAU - Suzuki, T
AU  - Suzuki T
FAU - Onishi, Y
AU  - Onishi Y
FAU - Morser, J
AU  - Morser J
FAU - Gabazza, E C
AU  - Gabazza EC
FAU - Takei, Y
AU  - Takei Y
FAU - Yano, Y
AU  - Yano Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Thromb Haemost
JT  - Journal of thrombosis and haemostasis : JTH
JID - 101170508
RN  - 0 (Biomarkers)
RN  - 0 (Chemokines)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Protein C)
RN  - 5W494URQ81 (Streptozocin)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Biomarkers/blood
MH  - Blood Pressure/drug effects
MH  - Chemokines/metabolism
MH  - Diabetes Mellitus, Experimental/chemically induced/complications/*drug therapy
MH  - Diabetic Nephropathies/blood/etiology/pathology/physiopathology/*prevention & 
      control
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Drug Administration Schedule
MH  - Fibrosis
MH  - Humans
MH  - Injections, Intraperitoneal
MH  - Intercellular Signaling Peptides and Proteins/metabolism
MH  - Kidney/*drug effects/metabolism/pathology/physiopathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nephrectomy
MH  - Nephrosclerosis/etiology/prevention & control
MH  - Organ Size/drug effects
MH  - Protein C/administration & dosage/*pharmacology
MH  - Streptozocin
MH  - Time Factors
EDAT- 2012/01/13 06:00
MHDA- 2013/07/09 06:00
CRDT- 2012/01/13 06:00
PHST- 2012/01/13 06:00 [entrez]
PHST- 2012/01/13 06:00 [pubmed]
PHST- 2013/07/09 06:00 [medline]
AID - S1538-7836(22)06205-5 [pii]
AID - 10.1111/j.1538-7836.2012.04621.x [doi]
PST - ppublish
SO  - J Thromb Haemost. 2012 Mar;10(3):337-46. doi: 10.1111/j.1538-7836.2012.04621.x.