Upregulation of connective tissue growth factor in a rat model of chronic allograft nephropathy.
OBJECTIVE
To study the expression of connective tissue growth factor (CTGF) in transplanted rat kidney and its relationship with chronic allograft nephropathy (CAN).


METHODS
Kidney transplantation was performed from Lewis to Fisher 344 allogeneic rat strain, and kidney grafts were harvested at the eighth, 12th and 16th week. The morphological changes were studied, and collagen deposition was determined by Masson trichrome stain. Serum creatinine was examined. The fibrotic process and the CAN grades were evaluated according to Banff 97 schema. The expressions of transforming growth factor beta, CTGF and alpha-smooth muscle actin were detected to assess the development of grafted kidney fibrosis and to discuss their relationships. Spearman correlation was used for correlation study between CTGF expression and development of CAN.


RESULTS
Serum creatinine was promoted in a time-dependent manner. Morphological changes suggested that the grafted kidneys were under abnormalities. At the end stage, focal segmental glomerulosclerosis was seen; tubular epithelial cells lost their phenotype and interstitial fibrosis was notable. Masson trichrome stain showed significant collagen accumulation in a time-dependent manner. Immunohistochemistry and western blotting results showed that the transforming growth factor beta, CTGF and alpha-smooth muscle actin expression were markedly promoted compared with the control group. CTGF was mainly expressed in the plasm of proximal tubular epithelial cells based on the severity of CAN.


CONCLUSIONS
Connective tissue growth factor might play an important role in the pathological changes of CAN after kidney transplantation. The expression of CTGF in epithelial cells could act as a molecular marker of interstitial fibrosis and CAN.
Tu
Zhidan
Z
Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, China.
Shi
Yujun
Y
Wang
Jinjing
J
Bao
Ji
J
Bu
Hong
H
D000199:Actins / Q000378:metabolism; D000818:Animals; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism; D055513:Connective Tissue Growth Factor; D004195:Disease Models, Animal; D005355:Fibrosis; D006084:Graft Rejection / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D017874:Immediate-Early Proteins / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D016030:Kidney Transplantation; D008297:Male; D009392:Nephrectomy; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014184:Transplantation, Homologous; D015854:Up-Regulation
D000199:Actins; D003094:Collagen; D055513:Connective Tissue Growth Factor; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta; C526316:CCN2 protein, rat; C498862:Acta2 protein, rat