Redistribution of connexin43 expression in glomerular podocytes predicts poor renal prognosis in patients with type 2 diabetes and overt nephropathy.
BACKGROUND
Significance of podocyte injury in the progression of diabetic nephropathy is not well-understood. In this study, we examined whether alteration of gap junction protein connexin43 (Cx43) expression in podocytes is associated with the progression of overt diabetic nephropathy.


METHODS
We recruited 29 type 2 diabetic patients with overt nephropathy who underwent renal biopsy. Nephrectomized kidney samples obtained from seven subjects with localized neoplasm and biopsy specimens from five patients diagnosed as minor glomerular abnormalities were used as controls. Cx43 staining on paraffin-embedded kidney sections were studied by immunohistochemistry.


RESULTS
In controls, Cx43 was expressed at podocytes in a linear pattern along the glomerular basement membrane. In contrast, downregulation and loss of uniformly linear staining of Cx43 (Cx43 heterogeneity) in podocytes were observed in diabetic nephropathy. Cx43 intensity correlated with current renal function (R = 0.647, P < 0.005), whereas the magnitude of Cx43 heterogeneity correlated well with the degree of future decline in renal function (R = -0.705, P < 0.001).


CONCLUSIONS
Alteration of Cx43 expression in podocytes was closely associated with the progression of overt diabetic nephropathy. These results indicate that change in Cx43 expression at podocytes represents a progressive stage in overt diabetic nephropathy and that it may be a convenient way to predict future decline in renal function.
Sawai
Kazutomo
K
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan. muko@kuhp.kyoto-u.ac.jp
Mukoyama
Masashi
M
Mori
Kiyoshi
K
Yokoi
Hideki
H
Koshikawa
Masao
M
Yoshioka
Tetsuro
T
Takeda
Ryuji
R
Sugawara
Akira
A
Kuwahara
Takashi
T
Saleem
Moin A
MA
Ogawa
Osamu
O
Nakao
Kazuwa
K
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D015153:Blotting, Western; D002478:Cells, Cultured; D018031:Connexin 43 / Q000096:biosynthesis*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies
D015415:Biomarkers; D018031:Connexin 43