Fibrocytes: a new insight into kidney fibrosis.
Fibrocytes are supposed to be a circulating connective tissue cell progenitor, which consists of a novel population of peripheral blood cells. This distinct population of blood-borne cells shares markers of leukocytes as well as mesenchymal cells. Accumulating evidence indicates that fibrosis is characteristic of progressive chronic kidney diseases of any etiologies, resulting in kidney failure. We have uncovered that CCR7-positive fibrocytes migrate into the kidney in response to secondary lymphoid tissue chemokine (SLC/CCL21) and contribute to kidney fibrosis induced by unilateral ureteral obstruction in mice. In addition, the blockade of CCL21/CCR7 signaling by anti-CCL21 antibodies reduced kidney fibrosis, which was confirmed by a decrease in fibrosis in CCR7-null mice with concomitant reduction in macrophage recruitment along with reduced renal transcripts of monocyte chemoattractant protein-1 (MCP-1/CCL2). These findings suggest that fibrocytes dependent on CCL21/CCR7 signaling pathways contribute to the pathogenesis of kidney fibrosis, thereby providing that regulating fibrocytes may provide a novel therapeutic benefit for kidney fibrosis.
Wada
T
T
Division of Blood Purification, Department of Disease Control and Homeostasis, Disease Control and Homeostasis, Kanazawa University, Kanazawa, Japan. twada@m-kanazawa.jp
Sakai
N
N
Matsushima
K
K
Kaneko
S
S
D000818:Animals; D002465:Cell Movement; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000502:physiology; D005355:Fibrosis; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D009395:Nephritis, Interstitial / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000502:physiology; D013234:Stem Cells
C515478:CCL21 protein, human; C515370:CCR7 protein, human; C515479:Ccl21c protein, mouse; C515371:Ccr7 protein, mouse; D054421:Chemokine CCL21; D019742:Chemokines, CC; D054400:Receptors, CCR7; D019707:Receptors, Chemokine