ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on Twitter

Kidney Week

Abstract: TH-PO377

C-C Chemokine Receptor 2 (CCR2) Genetic Deletion Protects Against Gadolinium-Induced Skin Lesions by Preventing Recruitment of Bone Marrow-Derived Fibrocytes in a Novel Mouse Model

Session Information

Category: Cell Biology

  • 201 Cell Signaling, Oxidative Stress


  • Wagner, Brent, South Texas Veterans Health Care System, San Antonio, Texas, United States
  • Tan, Chunyan, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Do, Catherine, South Texas Veterans Health Care System, San Antonio, Texas, United States
  • Drel, Viktor, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Lee, Doug Yoon, UTHSCSA, San Antonio, Texas, United States
  • Gorin, Yves C., University of Texas Health Science Center, San Antonio, Texas, United States

Gadolinium-based contrast is now associated with a number of conditions, including ‘nephrogenic’ systemic fibrosis/gadolinium-associated systemic fibrosis (NSF) and gadolinium deposition disease. Bone marrow-derived fibrocytes and the monocyte chemoattractant protein 1 (MCP1) inflammatory pathway have been implicated as mediators in rats but mechanistic studies in this model have been limited. In the present work, we establish a mouse models of NSF.


Lethally-irradiated mice with 5/6 nephrectomies were salvaged with bone marrow from green fluorescent protein- (GFP-) expressing donors. Next, GFP-positive marrow was transplanted into wild-type and mice deficient of the C-C chemokine receptor 2 (CCR2), the prime effector of MCP-1. After an engraftment period, recipients were randomized to control or gadolinium-based contrast treatment.


Dermal cellularity was increased in contrast-treated mice. Compared to control, skin GFP, fibronectin, and type I collagen were all increased in the contrast-treated animals as assessed by Western blot and immunofluorescence. Importantly, CD45RO, a marker for myeloid fibrocytes, was abundant in the dermis of contrast-treated animals, frequently expressed by the myeloid cells. Many of these cells expressed cytoplasmic α-smooth muscle cell actin, a marker of myofibroblast activation. Importantly, the markers of myofibroblast activation and fibrosis colocalized with GFP-positive cells in contrast-treated animals. MCP-1 and CCR-2 were increased in the tissues from contrast-treated mice. Recipients devoid of CCR2 had an abrogation of gadolinium-induced pathology and displayed fewer GFP-positive cells in the skin.


Systemic fibrosis can be induced by gadolinium contrast in mice. That GFP levels and expression increase in an involved organ, the skin, in tandem with a fibrocyte marker—CD45RO—supports the blood-borne circulating fibrocyte hypothesis of the disease. This is the first demonstration of fibrocyte trafficking ever demonstrated in mice. Importantly, similar to what is observed in a rat model, our data demonstrate that the monocyte chemoattractant protein 1/C-C chemokine receptor 2 axis plays a critical role in the pathogenesis of gadolinium-induced systemic fibrosis.


  • NIDDK Support