PXD006494

PXD006494 is an original dataset announced via ProteomeXchange.

Title	Proteomic profiling of TGFBIp-null mouse corneas reveals minor changes in the extracellular matrix composition supportive of TGFBI knockdown as therapy against TGFBI-linked corneal dystrophies
Description	TGFBIp is a constituent of the extracellular matrix in many human tissues including the cornea, where it is one of the most abundant proteins expressed. TGFBIp interacts with type I, II, IV, VI and XII collagens as well as several members of the integrin family, suggesting that it plays an important role in maintaining structural integrity and possibly corneal transparency as well. More than 60 point mutations in the TGFBI gene have been described in four types of corneal dystrophies (granular, lattice, Thiel-Behnke and Reis-Bückler). These defects are characterized by aberrant protein folding, leading to TGFBIp aggregation in the cornea and resulting in severe visual impairment and blindness. Several studies have focused on targeting TGFBIp expression in the cornea as a therapeutic approach to treat TGFBI-linked corneal dystrophies, but the effect of this approach on corneal homeostasis and integrity remained unknown. In the current study, we evaluated the histological and proteomic profiles of corneas from TGFBI-deficient mice as well as potential redundant functions of the paralogous protein periostin. The absence of TGFBIp in mouse corneas did not grossly affect the collagen scaffold, and periostin was unable to compensate for TGFBIp. However, a proteomic comparison of wild-type and TGFBI-/- mice revealed that 11 other proteins were differentially regulated, including type VI and XII collagens. Hence, the complete elimination of TGFBIp in the cornea as a treatment for TGFBI-linked corneal dystrophies may cause unintended consequences at the molecular level that are not evident at the macroscopic or functional levels.
HostingRepository	PRIDE
AnnounceDate	2017-11-14
AnnouncementXML	Submission_2017-11-14_08:48:38.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ebbe Toftgaard Poulsen
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2017-05-11 04:35:56	ID requested
⏵ 1	2017-11-14 08:48:39	announced

Poulsen ET, Runager K, Nielsen NS, Lukassen MV, Thomsen K, Snider P, Simmons O, Vorum H, Conway SJ, Enghild JJ, Proteomic profiling of TGFBI-null mouse corneas reveals only minor changes in matrix composition supportive of TGFBI knockdown as therapy against TGFBI-linked corneal dystrophies. FEBS J, 285(1):101-114(2018) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: Cornea, ECM, iTRAQ, LC-MS/MS, Periostin, TGFBIp

Jan J. Enghild
contact affiliation	Department of Molecular Biology and Genetics Aarhus Univerity Denmark
contact email	jje@mbg.au.dk
lab head
Ebbe Toftgaard Poulsen
contact affiliation	Department of Molecular Biology and Genetics
contact email	etp@mb.au.dk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD006494
     1. Label: PRIDE project
     2. Name: Proteomic profiling of TGFBIp-null mouse corneas reveals minor changes in the extracellular matrix composition supportive of TGFBI knockdown as therapy against TGFBI-linked corneal dystrophies