Abstract
Renal fibrosis represents a common pathway leading to progression of chronic kidney disease. Renal interstitial fibrosis is characterized by extensive fibroblast activation and excessive production and deposition of extracellular matrix (ECM), which leads to progressive loss of kidney function. There is no effective therapy available clinically to halt or even reverse renal fibrosis. Although activated fibroblasts/myofibroblasts are responsible for the excessive production and deposition of ECM, their origin remains controversial. Recent evidence suggests that bone marrow-derived fibroblast precursors contribute significantly to the pathogenesis of renal fibrosis. Understanding the molecular signaling mechanisms underlying the recruitment and activation of the bone marrow-derived fibroblast precursors will lead to novel therapy for the treatment of chronic kidney disease. In this review, we summarize recent advances in our understanding of the recruitment and activation of bone marrow-derived fibroblast precursors in the kidney and the development of renal fibrosis and highlights new insights that may lead to novel therapies to prevent or reverse the development of renal fibrosis.
Highlights
Chronic kidney disease (CKD) is a global public health problem
Using bone marrow transplantation of transgenic mice that express green fluorescence protein (GFP) driven by collagen 1A1 promoter, we have shown that bone marrow-derived hematopoietic fibroblasts migrate into the kidney, proliferate, and differentiate into α-smooth muscle actin (SMA)+ myofibroblasts (Xia et al, 2014b)
Our results have demonstrated that genetic deletion of CXCL16 protects the kidney from angiotensin II infusion-induced renal dysfunction, inhibits renal fibrosis, reduces proteinuria, suppresses bone marrow-derived fibroblast accumulation, myofibroblast formation, macrophage, and T cell infiltration and pro-inflammatory cytokine expression without affecting blood pressure at baseline or in response to angiotensin II infusion (Xia et al, 2013b)
Summary
Chronic kidney disease (CKD) is a global public health problem. Worldwide, over 1 million people die from CKD yearly. In rodent models of renal fibrosis, we and others have shown that bone marrow-derived fibroblasts migrate into the kidney in response to injury (Iwano et al, 2002; Roufosse et al, 2006; Broekema et al, 2007; Chen et al, 2011; Xia et al, 2014b). Using bone marrow transplantation of transgenic mice that express GFP driven by collagen 1A1 promoter, we have shown that bone marrow-derived hematopoietic fibroblasts migrate into the kidney, proliferate, and differentiate into α-SMA+ myofibroblasts (Xia et al, 2014b). Recent studies have shown that chemokines and their receptors play an important role in the recruitment of bone marrow-derived fibroblast precursors into the kidney in response to injury.
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