TY - JOUR
T1 - Bone marrow-derived cells play a major role in kidney fibrosis via proliferation and differentiation in the infiltrated site
AU - Jang, Hee Seong
AU - Kim, Jee In
AU - Jung, Kyong Jin
AU - Kim, Jinu
AU - Han, Ki Hwan
AU - Park, Kwon Moo
N1 - Funding Information:
This study was supported by a grant from the Korea Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea ( A111366 ).
PY - 2013/6
Y1 - 2013/6
N2 - Increase of interstitial cell population, resulting in the expansion of interstitium, excessive production of extracellular matrix, and reduction of functioning tubules, is critical in fibrotic progression in the kidney of patients suffering from chronic renal diseases. Here, we investigated the contribution of bone marrow-derived cells (BMDC) in kidney fibrosis caused by ureteral obstruction (UO) using eGFP bone marrow-reconstituted chimeric mice. UO caused dramatic increases in the numbers of interstitial cells and expansion of the interstitium. Most kidney interstitial cells expressed GFP. Twenty nine percent of interstitial cells were cells that had proliferated and approximately 89% among them were BMDCs. Proliferation of fibroblasts differentiated from BMDCs significantly occurred in the interstitium of UO-kidney. Removal of BMDCs by whole body irradiation after UO resulted in reduction of kidney fibrosis, while injection of RAW264.7 cells, monocytes/macrophages, into irradiated mice induced a reversal of this reduction. Treatment with apocynin, an inhibitor of NADPH oxidase, reduced infiltration of BMDCs into the UO-kidney, leading to reduction of kidney fibrosis. In addition, only a few slow-cycling cells were observed in the interstitium of normal kidney. Even after UO, no change in the number of those cells was observed. Our findings demonstrate that BMDCs are a major source for interstitial expansion during kidney fibrosis via infiltration into damaged sites, differentiation to fibroblasts, and subsequent proliferation, contributing kidney fibrosis. These data provide a clear therapeutic target for treatment of chronic kidney disease. •BMDCs occupy the majority of increased interstitial population in fibrotic kidney.•BMDCs differentiate into the cell that has characteristics of fibroblast and subsequently proliferate in fibrotic kidney.•Inhibition of BMDCs infiltration and production prevents the kidney fibrosis.•Interstitial slow-cycling cell may not participate in increased fibroblast population in fibrotic kidney.
AB - Increase of interstitial cell population, resulting in the expansion of interstitium, excessive production of extracellular matrix, and reduction of functioning tubules, is critical in fibrotic progression in the kidney of patients suffering from chronic renal diseases. Here, we investigated the contribution of bone marrow-derived cells (BMDC) in kidney fibrosis caused by ureteral obstruction (UO) using eGFP bone marrow-reconstituted chimeric mice. UO caused dramatic increases in the numbers of interstitial cells and expansion of the interstitium. Most kidney interstitial cells expressed GFP. Twenty nine percent of interstitial cells were cells that had proliferated and approximately 89% among them were BMDCs. Proliferation of fibroblasts differentiated from BMDCs significantly occurred in the interstitium of UO-kidney. Removal of BMDCs by whole body irradiation after UO resulted in reduction of kidney fibrosis, while injection of RAW264.7 cells, monocytes/macrophages, into irradiated mice induced a reversal of this reduction. Treatment with apocynin, an inhibitor of NADPH oxidase, reduced infiltration of BMDCs into the UO-kidney, leading to reduction of kidney fibrosis. In addition, only a few slow-cycling cells were observed in the interstitium of normal kidney. Even after UO, no change in the number of those cells was observed. Our findings demonstrate that BMDCs are a major source for interstitial expansion during kidney fibrosis via infiltration into damaged sites, differentiation to fibroblasts, and subsequent proliferation, contributing kidney fibrosis. These data provide a clear therapeutic target for treatment of chronic kidney disease. •BMDCs occupy the majority of increased interstitial population in fibrotic kidney.•BMDCs differentiate into the cell that has characteristics of fibroblast and subsequently proliferate in fibrotic kidney.•Inhibition of BMDCs infiltration and production prevents the kidney fibrosis.•Interstitial slow-cycling cell may not participate in increased fibroblast population in fibrotic kidney.
KW - Bone marrow-derived cell
KW - Differentiation
KW - Fibroblast
KW - Fibrosis
KW - Proliferation
KW - Reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=84875615221&partnerID=8YFLogxK
U2 - 10.1016/j.bbadis.2013.02.016
DO - 10.1016/j.bbadis.2013.02.016
M3 - Article
C2 - 23466592
AN - SCOPUS:84875615221
SN - 0925-4439
VL - 1832
SP - 817
EP - 825
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 6
ER -