The overall objective of the proposed research is to develop molecular therapies for pseudoxanthoma elasticum (PXE), a pleiotropic multisystem disorder affecting the skin, the eyes, and the cardiovascular system with progressive pathological mineralization of soft connective tissues, primarily the elastic structures. This heritable disease is caused by mutations in the ABCC6 gene, which is highly expressed in the liver and the kidneys and serves as a metabolic transmembrane transporter. The metabolic nature of PXE has been proven by our recent studies using a PXE mouse grafting and parabiosis models (see Preliminary Studies). However, there is no cure or effective treatment for PXE so far.

Public Health Relevance

The overall objective of the proposed research is to develop molecular therapies for pseudoxanthoma elasticum (PXE), a pleiotropic multisystem disorder affecting the skin, the eyes, and the cardiovascular system with progressive pathological mineralization of soft connective tissues, primarily the elastic structures.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AR057099-03
Application #
8290499
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Program Officer
Tseng, Hung H
Project Start
2010-07-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
3
Fiscal Year
2012
Total Cost
$116,627
Indirect Cost
$8,639
Name
Thomas Jefferson University
Department
Dermatology
Type
Schools of Medicine
DUNS #
053284659
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
Jin, Liang; Jiang, Qiujie; Wu, Zhengsheng et al. (2015) Genetic heterogeneity of pseudoxanthoma elasticum: the Chinese signature profile of ABCC6 and ENPP1 mutations. J Invest Dermatol 135:1294-302
Li, Qiaoli; Jiang, Qiujie; Uitto, Jouni (2014) Ectopic mineralization disorders of the extracellular matrix of connective tissue: molecular genetics and pathomechanisms of aberrant calcification. Matrix Biol 33:23-8
Zhou, Yong; Jiang, Qiujie; Takahagi, Shunsuke et al. (2013) Premature termination codon read-through in the ABCC6 gene: potential treatment for pseudoxanthoma elasticum. J Invest Dermatol 133:2672-7
Li, Q; Baker, J; Kowalczyk, J et al. (2013) Paediatric pseudoxanthoma elasticum with cardiovascular involvement. Br J Dermatol 169:1148-51
Jiang, Qiujie; Uitto, Jouni (2012) Restricting dietary magnesium accelerates ectopic connective tissue mineralization in a mouse model of pseudoxanthoma elasticum (Abcc6(-/-) ). Exp Dermatol 21:694-9
Jiang, Qiujie; Takahagi, Shunsuke; Uitto, Jouni (2012) Administration of bone marrow derived mesenchymal stem cells into the liver: potential to rescue pseudoxanthoma elasticum in a mouse model (Abcc6-/-). J Biomed Biotechnol 2012:818937
Fulop, Krisztina; Jiang, Qiujie; Wetering, Koen V D et al. (2011) ABCC6 does not transport vitamin K3-glutathione conjugate from the liver: relevance to pathomechanisms of pseudoxanthoma elasticum. Biochem Biophys Res Commun 415:468-71
Jiang, Qiujie; Quaynor, Benjamin; Sun, Alex et al. (2011) The Samd9L gene: transcriptional regulation and tissue-specific expression in mouse development. J Invest Dermatol 131:1428-34
Jiang, Qiujie; Li, Qiaoli; Grand-Pierre, Alix E et al. (2011) Administration of vitamin K does not counteract the ectopic mineralization of connective tissues in Abcc6 (-/-) mice, a model for pseudoxanthoma elasticum. Cell Cycle 10:701-7
Jiang, Qiujie; Oldenburg, Reid; Otsuru, Satoru et al. (2010) Parabiotic heterogenetic pairing of Abcc6-/-/Rag1-/- mice and their wild-type counterparts halts ectopic mineralization in a murine model of pseudoxanthoma elasticum. Am J Pathol 176:1855-62