PMID- 12969130
OWN - NLM
STAT- MEDLINE
DCOM- 20040505
LR  - 20191107
IS  - 0098-6577 (Print)
IS  - 0098-6577 (Linking)
IP  - 86
DP  - 2003 Oct
TI  - Renin-angiotensin system activation and interstitial inflammation in human 
      diabetic nephropathy.
PG  - S64-70
AB  - BACKGROUND: The molecular mechanisms of renal injury in diabetic nephropathy (DN) 
      are not completely understood, although inflammatory cells play a key role. The 
      renin-angiotensin system (RAS) is involved in kidney damage; however, few studies 
      have examined the localization of RAS components in human DN. Our aim was to 
      investigate in renal biopsies the expression of RAS and their correlation with 
      proinflammatory parameters and renal injury. METHODS: The biopsies from 10 
      patients with type 2 diabetes mellitus and overt nephropathy were studied for the 
      expression of RAS components by immunohistochemistry (IH). In addition, by 
      Southwestern histochemistry we studied the in situ detection of the activated 
      nuclear factor kappa B (NFkappaB), and by IH and/or in situ hybridization (ISH), 
      the expression of monocyte chemoattractant protein-1 (MCP-1) and regulated upon 
      activation, normal T cell expressed and secreted (RANTES), whose genes are 
      regulated by NFkappaB. RESULTS: Angiotensin-converting enzyme (ACE) 
      immunostaining was elevated in tubular cells and appeared in interstitial cells. 
      Elevated levels of angiotensin II (Ang II) immunostaining were observed in 
      tubular and infiltrating interstitial cells. There was also a down-regulation of 
      AT1 and up-regulation of AT2 receptors. An activation of NFkappaB and a marked 
      up-regulation of NFkappaB-dependent chemokines mainly in tubular cells was 
      observed. Elevated levels of NFkappaB, chemokines, and Ang II in tubules were 
      correlated with proteinuria and interstitial cell infiltration. CONCLUSIONS: Our 
      results show that in human DN, RAS components are modified in renal compartments, 
      showing elevated local Ang II production, activation of tubular cells, and 
      induction of proinflammatory parameters. These data suggest that Ang II 
      contributes to the renal inflammatory process, and may explain the molecular 
      mechanisms of the beneficial effect of RAS blockade.
FAU - Mezzano, Sergio
AU  - Mezzano S
AD  - Division of Nephrology, School of Medicine, Universidad Austral, Valdivia, Chile. 
      smezzano@uach.cl
FAU - Droguett, Alejandra
AU  - Droguett A
FAU - Burgos, M Eugenia
AU  - Burgos ME
FAU - Ardiles, Leopoldo G
AU  - Ardiles LG
FAU - Flores, Claudio A
AU  - Flores CA
FAU - Aros, Claudio A
AU  - Aros CA
FAU - Caorsi, Italo
AU  - Caorsi I
FAU - Vio, Carlos P
AU  - Vio CP
FAU - Ruiz-Ortega, Marta
AU  - Ruiz-Ortega M
FAU - Egido, Jesus
AU  - Egido J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int Suppl
JT  - Kidney international. Supplement
JID - 7508622
RN  - 0 (Chemokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (NF-kappa B)
SB  - IM
MH  - Chemokines/metabolism
MH  - Diabetic Nephropathies/*complications/*metabolism
MH  - Humans
MH  - In Vitro Techniques
MH  - Inflammation Mediators/metabolism
MH  - Kidney/metabolism/pathology
MH  - NF-kappa B/metabolism
MH  - Nephritis/*etiology/pathology
MH  - *Renin-Angiotensin System
MH  - Up-Regulation
EDAT- 2003/09/13 05:00
MHDA- 2004/05/07 05:00
CRDT- 2003/09/13 05:00
PHST- 2003/09/13 05:00 [pubmed]
PHST- 2004/05/07 05:00 [medline]
PHST- 2003/09/13 05:00 [entrez]
AID - S0085-2538(15)49633-4 [pii]
AID - 10.1046/j.1523-1755.64.s86.12.x [doi]
PST - ppublish
SO  - Kidney Int Suppl. 2003 Oct;(86):S64-70. doi: 10.1046/j.1523-1755.64.s86.12.x.