Interstitial expression of heat-shock protein 47 correlates with capillary deposition of complement split product C4d in chronic allograft nephropathy.
BACKGROUND
Chronic allograft nephropathy (CAN), associated with late-allograft dysfunction is caused by alloantigen-dependent and -independent mechanisms, and eventually leads to interstitial fibrosis (ci). Activation of complement cascade is considered to be a poor prognostic marker of graft survival. This study was designed to examine the relationship between the expression of C4d and heat-shock protein 47 (HSP47, a collagen-specific chaperone) in the development of interstitial fibroproliferative lesions in CAN.


METHODS
Sixty-three renal allograft biopsy specimens, obtained from 48 patients, were examined for the expression of C4d, HSP47, CD68 and alpha-smooth muscle actin (alpha-SMA) by immunohistochemistry. Double-staining was performed to determine the colocalization of C4d and HSP47. The relationship of between the expression of C4d, HSP47, CD68 and alpha-SMA and the clinical and histopathological parameters were statistically analysed.


RESULTS
No expression of C4d was noted in the tubulointerstitium including peritubular capillary (PTC) of the control kidney. C4d was expressed in PTC in one-third of allograft renal tissues with morphological evidences of CAN. The interstitial cells around the fibrotic areas of the PTC of CAN were positive for the expression of HSP47. The deposition of C4d in PTC correlated with interstitial expression of HSP47 around the PTC. Most HSP47 expressing cells were phenotypically altered myofibroblasts, as determined by the dual staining of alpha-SMA.


CONCLUSIONS
The increased expression of HSP47 positively correlated with the expression of C4d in PTC, and might contribute to the progression of interstitial ci in CAN.
Ohba
Kojiro
K
Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Miyata
Yasuyoshi
Y
Koga
Shigehiko
S
Nishikido
Masaharu
M
Kanetake
Hiroshi
H
Nazneen
Arifa
A
Razzaque
Mohammed S
MS
Taguchi
Takashi
T
D000293:Adolescent; D000328:Adult; D002196:Capillaries / Q000378:metabolism; D015935:Complement C4b / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006084:Graft Rejection / Q000378:metabolism*; D050958:HSP47 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007672:Kidney Cortex / Q000378:metabolism; D007674:Kidney Diseases; D016030:Kidney Transplantation / Q000276:immunology*; D007684:Kidney Tubules / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism*; D014184:Transplantation, Homologous
D050958:HSP47 Heat-Shock Proteins; D010446:Peptide Fragments; C494660:SERPINH1 protein, human; D015935:Complement C4b; C032261:complement C4d