Xiao-Hui Niu1,2,3, Yun-Peng Xie1, Song Yang2, Yanchun Chen2, Liang Xu2, Ying Zhang4, Yang Liu5. 1. Institute of Cardiovascular Diseases, The First Affiliated Hospital of Dalian Medical University, No 222, Zhongshan Rd, Dalian, China. 2. Yixing People's Hospital, The Affiliated Hospital of Jiangsu University, Yixing, China. 3. Department of Cardiology, the First Affiliated Hospital of Dalian Medical University, No 222, Zhongshan Rd, Dalian, China. 4. Department of Cardiology, the First Affiliated Hospital of Dalian Medical University, No 222, Zhongshan Rd, Dalian, China. zy114129@sina.com. 5. Institute of Cardiovascular Diseases, The First Affiliated Hospital of Dalian Medical University, No 222, Zhongshan Rd, Dalian, China. liuyang19831119@163.com.
Abstract
BACKGROUND: Fibrosis in multiple organs increases with age. Circulating fibrocytes are bone-marrow-derived mesenchymal progenitors that contribute to heart, lung, and kidney fibrosis under the diseased conditions. Whether circulating fibrocytes contribute to aging-related fibrosis is very limited. METHODS AND RESULTS: We measured the proportion and differentiation of circulating fibrocytes (CD45+/CD34+/collagen I+) from elders (n = 12) and adults (n = 12) using flow cytometry. Differentiated fibrocytes in the culture dishes were isolated and microarray was performed. The percentage of circulating fibrocytes in elders (1.95 ± 0.43%) was comparable to that in the adults (1.71 ± 0.38%). Cultured fibrocytes displayed enhanced potential of differentiation in the elder group (67.91 ± 5.88%) vs the adult group (44.03 ± 7.98%). In addition, expression of fibroblast activation markers and cell migratory ability were also increased in differentiated fibrocytes from elders. Microarray analysis revealed that differentiated fibrocytes from elders expressed high level of interleukin-18 (IL-18) receptor 1 (IL-18R1). Furthermore, we found IL-18 was elevated in the plasma of elders and IL-18/IL-18R1 was shown to promote fibrocyte differentiation. CONCLUSION: Circulating fibrocytes from elders had an enhanced capacity to differentiate into myofibroblasts, and might contribute to age-dependent fibrosis. Age-dependent increment of differentiation at least in part arose from their enhanced expression of IL-18R1. Inhibiting fibrocyte differentiation might be useful as an adjuvant treatment to delay the fibrosis process in aging population.
BACKGROUND:Fibrosis in multiple organs increases with age. Circulating fibrocytes are bone-marrow-derived mesenchymal progenitors that contribute to heart, lung, and kidney fibrosis under the diseased conditions. Whether circulating fibrocytes contribute to aging-related fibrosis is very limited. METHODS AND RESULTS: We measured the proportion and differentiation of circulating fibrocytes (CD45+/CD34+/collagen I+) from elders (n = 12) and adults (n = 12) using flow cytometry. Differentiated fibrocytes in the culture dishes were isolated and microarray was performed. The percentage of circulating fibrocytes in elders (1.95 ± 0.43%) was comparable to that in the adults (1.71 ± 0.38%). Cultured fibrocytes displayed enhanced potential of differentiation in the elder group (67.91 ± 5.88%) vs the adult group (44.03 ± 7.98%). In addition, expression of fibroblast activation markers and cell migratory ability were also increased in differentiated fibrocytes from elders. Microarray analysis revealed that differentiated fibrocytes from elders expressed high level of interleukin-18 (IL-18) receptor 1 (IL-18R1). Furthermore, we found IL-18 was elevated in the plasma of elders and IL-18/IL-18R1 was shown to promote fibrocyte differentiation. CONCLUSION: Circulating fibrocytes from elders had an enhanced capacity to differentiate into myofibroblasts, and might contribute to age-dependent fibrosis. Age-dependent increment of differentiation at least in part arose from their enhanced expression of IL-18R1. Inhibiting fibrocyte differentiation might be useful as an adjuvant treatment to delay the fibrosis process in aging population.
Authors: Amanda J Lee; Branson Chen; Marianne V Chew; Nicole G Barra; Mira M Shenouda; Tina Nham; Nico van Rooijen; Manel Jordana; Karen L Mossman; Robert D Schreiber; Matthias Mack; Ali A Ashkar Journal: J Exp Med Date: 2017-03-06 Impact factor: 14.307