PMID- 23656889
OWN - NLM
STAT- MEDLINE
DCOM- 20131001
LR  - 20220309
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 62
IP  - 8
DP  - 2013 Aug
TI  - Blockade of KCa3.1 ameliorates renal fibrosis through the TGF-beta1/Smad pathway in 
      diabetic mice.
PG  - 2923-34
LID - 10.2337/db13-0135 [doi]
AB  - The Ca(2+)-activated K(+) channel KCa3.1 mediates cellular signaling processes 
      associated with dysfunction of vasculature. However, the role of KCa3.1 in 
      diabetic nephropathy is unknown. We sought to assess whether KCa3.1 mediates the 
      development of renal fibrosis in two animal models of diabetic nephropathy. 
      Wild-type and KCa3.1(-/-) mice, and secondly eNOS(-/-) mice, had diabetes induced 
      with streptozotocin and then were treated with/without a selective inhibitor of 
      KCa3.1 (TRAM34). Our results show that the albumin-to-creatinine ratio 
      significantly decreased in diabetic KCa3.1(-/-) mice compared with diabetic 
      wild-type mice and in diabetic eNOS(-/-) mice treated with TRAM34 compared with 
      diabetic mice. The expression of monocyte chemoattractant protein-1 (MCP-1), 
      intercellular adhesion molecule 1 (ICAM1), F4/80, plasminogen activator inhibitor 
      type 1 (PAI-1), and type III and IV collagen significantly decreased (P < 0.01) 
      in kidneys of diabetic KCa3.1(-/-) mice compared with diabetic wild-type mice. 
      Similarly, TRAM34 reduced the expression of the inflammatory and fibrotic markers 
      described above in diabetic eNOS(-/-) mice. Furthermore, blocking the KCa3.1 
      channel in both animal models led to a reduction of transforming growth factor-beta1 
      (TGF-beta1) and TGF-beta1 type II receptor (TbetaRII) and phosphorylation of Smad2/3. Our 
      results provide evidence that KCa3.1 mediates renal fibrosis in diabetic 
      nephropathy through the TGF-beta1/Smad signaling pathway. Blockade of KCa3.1 may be 
      a novel target for therapeutic intervention in patients with diabetic 
      nephropathy.
FAU - Huang, Chunling
AU  - Huang C
AD  - Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney Medical 
      School, and University of Sydney, St Leonards, Sydney, New South Wales, 
      Australia.
FAU - Shen, Sylvie
AU  - Shen S
FAU - Ma, Qing
AU  - Ma Q
FAU - Chen, Jason
AU  - Chen J
FAU - Gill, Anthony
AU  - Gill A
FAU - Pollock, Carol A
AU  - Pollock CA
FAU - Chen, Xin-Ming
AU  - Chen XM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130508
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Chemokine CCL2)
RN  - 0 (Collagen Type IV)
RN  - 0 (Intermediate-Conductance Calcium-Activated Potassium Channels)
RN  - 0 (Kcnn4 protein, mouse)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (Pyrazoles)
RN  - 0 (Receptors, Transforming Growth Factor beta)
RN  - 0 (Smad Proteins)
RN  - 0 (TRAM 34)
RN  - 0 (Transforming Growth Factor beta1)
SB  - IM
CIN - Diabetes. 2013 Aug;62(8):2648-50. PMID: 23881192
MH  - Animals
MH  - Chemokine CCL2/metabolism
MH  - Collagen Type IV/metabolism
MH  - Diabetes Mellitus, Experimental/metabolism/*pathology
MH  - Diabetic Nephropathies/*drug therapy/metabolism/pathology
MH  - Fibrosis
MH  - Humans
MH  - Intermediate-Conductance Calcium-Activated Potassium Channels/*antagonists & 
      inhibitors/genetics/metabolism
MH  - Kidney/drug effects/metabolism/pathology
MH  - Mice
MH  - Mice, Knockout
MH  - Plasminogen Activator Inhibitor 1/metabolism
MH  - Pyrazoles/pharmacology/*therapeutic use
MH  - Receptors, Transforming Growth Factor beta/metabolism
MH  - Signal Transduction/drug effects/physiology
MH  - Smad Proteins/*metabolism
MH  - Transforming Growth Factor beta1/*metabolism
PMC - PMC3717839
EDAT- 2013/05/10 06:00
MHDA- 2013/10/18 06:00
PMCR- 2014/08/01
CRDT- 2013/05/10 06:00
PHST- 2013/05/10 06:00 [entrez]
PHST- 2013/05/10 06:00 [pubmed]
PHST- 2013/10/18 06:00 [medline]
PHST- 2014/08/01 00:00 [pmc-release]
AID - db13-0135 [pii]
AID - 0135 [pii]
AID - 10.2337/db13-0135 [doi]
PST - ppublish
SO  - Diabetes. 2013 Aug;62(8):2923-34. doi: 10.2337/db13-0135. Epub 2013 May 8.