This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The response to injury, whether it is restenosis after balloon angioplasty, or pulmonary or renal fibrosis due to chronic inflammation, results in increased accumulation of extracellular matrix (ECM) components with detrimental effects on tissue structure and function. This response involves the activation of fibroblasts termed myofibroblasts based on their characteristic expression of smooth muscle alpha-actin. As part of this wound healing response, these myofibroblasts proliferate, migrate, and produce abundant ECM including collagen type I and type III, as well as other ECM molecules. Dr. Lindner has identified a novel secreted 28 kDa protein called Collagen triple helix repeat containing 1 (Cthrc1) in a screen of differentially expressed sequences in balloon-injured versus normal vessels. Cthrc1 is highly expressed in medial smooth muscle cells and adventitial fibroblasts two weeks after vascular injury but expression declines by 4 weeks post-injury. Over expression of Cthrc1 in vascular smooth muscle cells results in decreased cell migration and reduced collagen matrix deposition. These exciting results suggest that Cthrc1 may have a regulatory role in the fibrotic response to injury and perhaps chronic inflammation. The proposed studies will provide significant new insights into the regulation of the fibrotic response in several organ systems, most importantly the vessel wall. These studies have translational potential for antifibrotic strategies.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Exploratory Grants (P20)
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Special Emphasis Panel (ZRR1-RI-8 (01))
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Maine Medical Center
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Soley, Luna; Falank, Carolyne; Reagan, Michaela R (2017) MicroRNA Transfer Between Bone Marrow Adipose and Multiple Myeloma Cells. Curr Osteoporos Rep 15:162-170
Young, K; Krebs, L T; Tweedie, E et al. (2016) Endoglin is required in Pax3-derived cells for embryonic blood vessel formation. Dev Biol 409:95-105
Ames, Jacquelyn J; Contois, Liangru; Caron, Jennifer M et al. (2016) Identification of an Endogenously Generated Cryptic Collagen Epitope (XL313) That May Selectively Regulate Angiogenesis by an Integrin Yes-associated Protein (YAP) Mechano-transduction Pathway. J Biol Chem 291:2731-50
Contois, Liangru W; Akalu, Abebe; Caron, Jennifer M et al. (2015) Inhibition of tumor-associated ?v?3 integrin regulates the angiogenic switch by enhancing expression of IGFBP-4 leading to reduced melanoma growth and angiogenesis in vivo. Angiogenesis 18:31-46
Motyl, Katherine J; Bishop, Kathleen A; DeMambro, Victoria E et al. (2013) Altered thermogenesis and impaired bone remodeling in Misty mice. J Bone Miner Res 28:1885-97
Apra, Caroline; Richard, Laurence; Coulpier, Fanny et al. (2012) Cthrc1 is a negative regulator of myelination in Schwann cells. Glia 60:393-403
Contois, Liangru W; Nugent, Desiree P; Caron, Jennifer M et al. (2012) Insulin-like growth factor binding protein-4 differentially inhibits growth factor-induced angiogenesis. J Biol Chem 287:1779-89
Urs, Sumithra; Henderson, Terry; Le, Phuong et al. (2012) Tissue-specific expression of Sprouty1 in mice protects against high-fat diet-induced fat accumulation, bone loss and metabolic dysfunction. Br J Nutr 108:1025-33
Sathyanarayana, Pradeep; Dev, Arvind; Pradeep, Anamika et al. (2012) Spry1 as a novel regulator of erythropoiesis, EPO/EPOR target, and suppressor of JAK2. Blood 119:5522-31
Motyl, Katherine J; Dick-de-Paula, Ingrid; Maloney, Ann E et al. (2012) Trabecular bone loss after administration of the second-generation antipsychotic risperidone is independent of weight gain. Bone 50:490-8

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