Correlations of tissue macrophages and cytoskeletal protein expression with renal fibrosis in patients with diabetes mellitus.
BACKGROUND
In clinicopathological studies of cellular remodeling in the progression of diabetic nephropathy, it has not been well described whether tissue macrophage numbers and the expression of two cytoskeletal proteins--alpha-smooth muscle actin (alphaSMA) and vimentin--correlate with the disease severity.


METHODS
Renal biopsy specimens from 23 patients with noninsulin-dependent diabetes mellitus (NIDDM) were examined by immunoperoxidase methods for CD68+ macrophages and alphaSMA and vimentin staining in paraffin-embedded samples. alphaSMA staining was evaluated in mesangial and interstitial myofibroblastic cells, and vimentin staining was evaluated in podocytes and mesangial and tubular cells.


RESULTS
Glomerular macrophage numbers were not correlated with any clinicopathological scores. However, the interstitial macrophage score was significantly correlated with serum creatinine (sCr) and strongly correlated with the interstitial fibrosis score. Both alphaSMA and vimentin were detectable in the mesangium, without significant correlation with each other. A positive correlation was observed between mesangial alphaSMA and urinary (u-) protein levels. In contrast, an inverse correlation was observed between levels of mesangial vimentin and u-protein. Mesangial alphaSMA, but not vimentin, showed a significant correlation with glomerular sclerosis. Podocytic vimentin levels tended to decrease in patients with higher sCr levels. The severity of interstitial peritubular alphaSMA was correlated strongly with interstitial macrophage proliferation and significantly with the interstitial fibrosis score.


CONCLUSIONS
The expression of mesangial alphaSMA may play a role in the progression of glomerular damage, while, on the other hand, newly acquired mesangial vimentin seems to be attenuated by heavy proteinuria. In addition, it was suggested that peritubular alphaSMA-positive myofibroblastic cells, in collaboration with interstitial macrophages, contribute to the progression of interstitial fibrosis in diabetic nephropathy.
Yonemoto
Satomi
S
Division of Nephrology, Medical Research Institute Kitano Hospital, Osaka, and University of Fukui Hospital, Japan.
Machiguchi
Toshihiko
T
Nomura
Keiko
K
Minakata
Tamotsu
T
Nanno
Masataka
M
Yoshida
Haruyoshi
H
D000199:Actins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005355:Fibrosis; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000276:immunology / Q000473:pathology*; D008297:Male; D050199:Podocytes / Q000378:metabolism / Q000473:pathology; D012720:Severity of Illness Index; D014746:Vimentin / Q000235:genetics / Q000378:metabolism*; D000097382:CD68 Molecule
D000199:Actins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D003404:Creatinine; D014746:Vimentin; C067980:CD68 antigen, human; D000097382:CD68 Molecule