title: Distribution and expression of fibroblast-specific protein chemokine CCL21 and chemokine receptor CCR7 in renal allografts.
abstract: We aimed to characterize the expression and distribution of the fibroblast surface protein (FSP), the chemokine CC-ligand 21 (CCL21) secondary lymphoid tissue chemokine CC-chemokine receptor 7 (CCR7) in renal allograft biopsy specimens obtained from patients after transplantation. We recruited 165 patients who received renal transplants at our center for this study. Histological examination of the renal allograft biopsy specimens was performed using hematoxylin-eosin, periodic acid-Schiff, and Masson's trichrome staining. Distribution and expression of FSP, CCL21, and CCR7 were determined using immunohistochemistry staining. Serum creatinine levels were evaluated using an enzymatic sarcosine oxidase method. FSP was mainly localized in the cytoplasm and nucleus of renal interstitial fibroblasts and tubular epithelial cells. Compared with the normal group, an elevated number of FSP-positive fibroblasts were observed in patients with acute/active cellular rejection and chronic/sclerosing allograft nephropathy (P < .05). Patients with chronic/sclerosing allograft nephropathy also showed increased total fibroblasts as compared with borderline changes (P < .05). In a multiple regression analysis, CCR7-positive expression was a strong protective factor for acute/active cellular rejection and recurrent nephropathy (odds ratio [OR] = 0.12, P = .034, and OR = 0.08; P = .036, respectively). In contrast, CCL21-positive expression led to a high susceptibility to recurrent nephropathy among renal transplant patients (OR = 10.41, P = .029). Moreover, FSP and CCL21, or CCL21 and CCR7 were localized in the interstitial fibroblasts and renal tubular epithelium cells. In addition, FSP and CCL21 expression positively correlated with serum creatinine levels. Our results suggested that the CCL21/CCR7 signaling pathway is involved in renal fibrosis in kidney transplant patients. An increased number of FSP-positive fibroblasts may be a risk factor for acute/active cellular rejection and chronic/sclerosing allograft nephropathy after renal transplantation. These findings may help understanding of renal allograft fibrosis.
authors.affiliation: Urinary System Disease Center, the First Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: H-L
authors.initials: HL
authors.lastname: Zhou
authors.forename: Y-T
authors.initials: YT
authors.lastname: Wang
authors.forename: T
authors.initials: T
authors.lastname: Gao
authors.forename: W-G
authors.initials: WG
authors.lastname: Wang
authors.forename: Y-S
authors.initials: YS
authors.lastname: Wang
mesh_terms: D000208:Acute Disease; D001706:Biopsy; D016022:Case-Control Studies; D054421:Chemokine CCL21 / Q000032:analysis*; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000276:immunology* / Q000473:pathology; D005355:Fibrosis; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006085:Graft Survival; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000276:immunology* / Q000473:pathology / Q000601:surgery*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D054400:Receptors, CCR7 / Q000032:analysis*; D012307:Risk Factors; D012598:Sclerosis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C515478:CCL21 protein, human; C515370:CCR7 protein, human; D054421:Chemokine CCL21; D054400:Receptors, CCR7; D003404:Creatinine