PMID- 14531804
OWN - NLM
STAT- MEDLINE
DCOM- 20040624
LR  - 20220227
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 64
IP  - 5
DP  - 2003 Nov
TI  - Activation of the TGF-beta/Smad signaling pathway in focal segmental 
      glomerulosclerosis.
PG  - 1715-21
AB  - BACKGROUND: Although the pathogenetic relevance of transforming growth 
      factor-beta (TGF-beta) to glomerulosclerosis is well established, it is not known 
      whether a signal transduction cascade of TGF-beta is involved in the development 
      of focal segmental glomerulosclerosis (FSGS), nor is it clear how TGF-beta 1 is 
      activated during the course of FSGS formation. METHODS: We examined the 
      expression patterns of TGF-beta 1, thrombospondin-1 (TSP-1), TGF-beta type II 
      receptor (TGF-beta IIR), phosphorylated Smad2/Smad3, and podocyte-specific 
      epitopes [Wilms' tumor protein-1 (WT-1) and glomerular epithelial protein-1 
      (GLEPP-1)] in 15 renal biopsy specimens with idiopathic FSGS and six renal 
      biopsies with no detectable abnormalities by means of immunohistochemistry. The 
      mRNA expression patterns of TGF-beta 1, TGF-beta IIR, and TSP-1 were further 
      evaluated by in situ hybridization in seven biopsies. RESULTS: In the controls, 
      immunostaining for TGF-beta 1, TSP-1, TGF-beta IIR, and phosphorylated 
      Smad2/Smad3 was almost negligible, but an apparent signal for TGF-beta 1, TSP-1, 
      and TGF-beta IIR mRNAs was observed in the visceral glomerular epithelial cells 
      (GEC). In the cases of FSGS, the expression levels of TGF-beta 1, TSP-1, and 
      TGF-betaIIR proteins and mRNAs and phosphorylated Smad2/Smad3 were significantly 
      increased, particularly in the GEC of the sclerotic segments, wherein WT-1 and 
      GLEPP-1 were not detected. CONCLUSION: These results suggest that damage to 
      podocyes may stimulate TGF-beta 1, TSP-1, and TGF-beta IIR expression in GEC, 
      thereby activating the Smad signaling pathway and, in so doing, leading to 
      overproduction of the extracellular matrix (ECM). Thus, a signal transduction 
      cascade of the TGF-beta/Smad signaling pathway, which is activated in the GEC, 
      appears to be involved in the development of FSGS.
FAU - Kim, Ji Hoon
AU  - Kim JH
AD  - Department of Pathology, Seoul National University College of Medicine, Seoul, 
      Korea.
FAU - Kim, Byoung Kwon
AU  - Kim BK
FAU - Moon, Kyung Chul
AU  - Moon KC
FAU - Hong, Hye Kyoung
AU  - Hong HK
FAU - Lee, Hyun Soon
AU  - Lee HS
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Transforming Growth Factor beta)
RN  - 0 (SMAD2 protein, human)
RN  - 0 (SMAD3 protein, human)
RN  - 0 (Smad2 Protein)
RN  - 0 (Smad3 Protein)
RN  - 0 (TGFB1 protein, human)
RN  - 0 (Thrombospondin 1)
RN  - 0 (Trans-Activators)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type II)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Child
MH  - DNA-Binding Proteins/*metabolism
MH  - Female
MH  - Glomerulosclerosis, Focal Segmental/*metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - Male
MH  - Middle Aged
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases
MH  - RNA, Messenger/analysis
MH  - Receptor, Transforming Growth Factor-beta Type II
MH  - Receptors, Transforming Growth Factor beta/genetics/metabolism
MH  - Signal Transduction/*physiology
MH  - Smad2 Protein
MH  - Smad3 Protein
MH  - Thrombospondin 1/genetics/metabolism
MH  - Trans-Activators/*metabolism
MH  - Transforming Growth Factor beta/genetics/*metabolism
MH  - Transforming Growth Factor beta1
EDAT- 2003/10/09 05:00
MHDA- 2004/06/25 05:00
CRDT- 2003/10/09 05:00
PHST- 2003/10/09 05:00 [pubmed]
PHST- 2004/06/25 05:00 [medline]
PHST- 2003/10/09 05:00 [entrez]
AID - S0085-2538(15)49522-5 [pii]
AID - 10.1046/j.1523-1755.2003.00288.x [doi]
PST - ppublish
SO  - Kidney Int. 2003 Nov;64(5):1715-21. doi: 10.1046/j.1523-1755.2003.00288.x.