BACKGROUND: Nuclear factor-kappaB (NF-kappaB) regulates genes involved in renal disease progression, such as the chemokines monocyte chemoattractant protein-1 (MCP-1) and RANTES. NF-kappaB is activated in experimental models of renal injury, and in vitro studies also suggest that proteinuria and angiotensin II could be important NF-kappaB activators. It has been proposed that locally produced MCP-1 may be involved in the development of diabetic nephropathy (DN). We examined the hypothesis that NF-kappaB could be an indicator of renal damage progression in DN. METHODS: Biopsy specimens from 11 patients with type 2 diabeties and overt nephropathy were studied by southwestern histochemistry for the in situ detection of activated NF-kappaB. In addition, by immunohistochemistry and/or in situ hybridization, we studied the expression of MCP-1 and RANTES, whose genes are regulated by NF-kappaB. RESULTS: NF-kappaB was detected mainly in cortical tubular epithelial cells and, to a lesser extent, in some glomerular and interstitial cells. A strong upregulation of MCP-1 and RANTES was observed in all the cases, mainly in tubular cells, and there was a strong correlation between the expression of these chemokines and NF-kappaB activation in the same cells, as observed in serial sections (r = 0.7; P = 0.01). In addition, the tubular expression of these chemokines was correlated mainly with the magnitude of the proteinuria (P = 0.002) and with interstitial cell infiltration (P<0.05). CONCLUSIONS: The activation of NF-kappaB and the transcription of certain pro-inflammatory chemokines in tubular epithelial cells are markers of progressive DN. Proteinuria might be one of the main factors inducing the observed pro-inflammatory phenotype.
BACKGROUND:Nuclear factor-kappaB (NF-kappaB) regulates genes involved in renal disease progression, such as the chemokines monocyte chemoattractant protein-1 (MCP-1) and RANTES. NF-kappaB is activated in experimental models of renal injury, and in vitro studies also suggest that proteinuria and angiotensin II could be important NF-kappaB activators. It has been proposed that locally produced MCP-1 may be involved in the development of diabetic nephropathy (DN). We examined the hypothesis that NF-kappaB could be an indicator of renal damage progression in DN. METHODS: Biopsy specimens from 11 patients with type 2 diabeties and overt nephropathy were studied by southwestern histochemistry for the in situ detection of activated NF-kappaB. In addition, by immunohistochemistry and/or in situ hybridization, we studied the expression of MCP-1 and RANTES, whose genes are regulated by NF-kappaB. RESULTS:NF-kappaB was detected mainly in cortical tubular epithelial cells and, to a lesser extent, in some glomerular and interstitial cells. A strong upregulation of MCP-1 and RANTES was observed in all the cases, mainly in tubular cells, and there was a strong correlation between the expression of these chemokines and NF-kappaB activation in the same cells, as observed in serial sections (r = 0.7; P = 0.01). In addition, the tubular expression of these chemokines was correlated mainly with the magnitude of the proteinuria (P = 0.002) and with interstitial cell infiltration (P<0.05). CONCLUSIONS: The activation of NF-kappaB and the transcription of certain pro-inflammatory chemokines in tubular epithelial cells are markers of progressive DN. Proteinuria might be one of the main factors inducing the observed pro-inflammatory phenotype.
Authors: Xiang-Lin Tan; Kalyan K Bhattacharyya; Shamit K Dutta; William R Bamlet; Kari G Rabe; Enfeng Wang; Thomas C Smyrk; Ann L Oberg; Gloria M Petersen; Debabrata Mukhopadhyay Journal: Pancreas Date: 2015-05 Impact factor: 3.327
Authors: Gudeta D Fufaa; E Jennifer Weil; Robert G Nelson; Robert L Hanson; William C Knowler; Brad H Rovin; Haifeng Wu; Jon B Klein; Theodore E Mifflin; Harold I Feldman; Ramachandran S Vasan; Paul L Kimmel; John W Kusek; Michael Mauer Journal: Nephrol Dial Transplant Date: 2015-02-03 Impact factor: 5.992
Authors: Francis U Umeoguaju; Benson C Ephraim-Emmanuel; Joy O Uba; Grace E Bekibele; Nwondah Chigozie; Orish Ebere Orisakwe Journal: Front Immunol Date: 2021-05-10 Impact factor: 7.561
Authors: Jeffrey J Olearczyk; Jeffrey E Quigley; Bradford C Mitchell; Tatsuo Yamamoto; In-Hae Kim; John W Newman; Ayala Luria; Bruce D Hammock; John D Imig Journal: Clin Sci (Lond) Date: 2009-01 Impact factor: 6.124