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Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):14098-103. Epub 2006 Sep 11.

Secondary lymphoid tissue chemokine (SLC/CCL21)/CCR7 signaling regulates fibrocytes in renal fibrosis.

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  • 1Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, and Division of Blood Purification, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.


Fibrocytes are a distinct population of bloodborne cells that share markers of leukocytes as well as mesenchymal cells. We hypothesized that CCR7-positive fibrocytes migrate into the kidney in response to secondary lymphoid tissue chemokine (SLC/CCL21) and contribute to renal fibrosis. To investigate this hypothesis, renal fibrosis was induced by unilateral ureteral obstruction in mice. A considerable number of fibrocytes dual-positive for CD45 and type I collagen (ColI) or CD34 and ColI infiltrated the interstitium, reaching a peak on day 7. Most fibrocytes were positive for CCR7, and CCL21/CCR7 blockade reduced the number of infiltrating fibrocytes. CCL21 and MECA79 dual-positive vessels were also detected in the interstitium. The blockade of CCL21/CCR7 signaling by anti-CCL21 antibodies reduced renal fibrosis, which was confirmed by a decrease in fibrosis in CCR7-null mice with concomitant reduction in renal transcripts of pro alpha1 chain of ColI and TGF-beta1. The number of F4/80-positive macrophages decreased along with renal transcripts of monocyte chemoattractant protein 1 (MCP-1/CCL2) after the blockade of CCL21/CCR7 signaling. These findings suggest that CCR7-positive fibrocytes infiltrate the kidney via CCL21-positive vessels, thereby contributing to the pathogenesis of renal fibrosis. Thus, the CCL21/CCR7 signaling of fibrocytes may provide therapeutic targets for combating renal fibrosis.

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