PXD047320

PXD047320 is an original dataset announced via ProteomeXchange.

Title	Administration of recombinant HSP47 as a new therapeutic approach to stimulate collagen secretion and ameliorate ECM in osteogenesis imperfecta
Description	Collagen misfolding, reduced collagen secretion and incorporation into the extracellular matrix, and impaired collagen organization are common features both in a physiological condition like aging and in pathological conditions like genetic diseases caused by defects in collagen or collagen related genes. Osteogenesis imperfecta (OI) is the prototype of collagen disorders since it is mainly caused by mutations in genes responsible for the synthesis and post translational modification of collagen type I, the most abundant protein of our body and of our skeleton. OI probands show reduced bone mass, bone deformations, and increased bone fragility associated to frequent fractures, but they do not benefit from specific treatments. Here the therapeutic potential of heat shock protein 47 (HSP47), the collagen specific chaperone and a key endogenous player in collagen secretion, was tested in OI probands primary fibroblast lines. Administration of exogenous HSP47, that is able to be uptaken by the cell and to localize with both cis Golgi and secretory pathway sites, increased collagen secretion, reduced intracellular procollagen I retention and ameliorated the general ER proteostasis, leading to a substantial improvement in cellular homeostasis and vitality. These positive changes were also mirrored by an increased content into the OI proband matrix of collagen I. Efficacy of exogenous HSP47 was then proved in vivo on the bone phenotype of the zebrafish p3h1-/- OI model. Methods Collection samples nLC‑MS/MS analysis was used to assess hydroxylation and O-Glycosylation on lysine sites of type I collagen. Extracted collagen from control, OI and HS47 probands fibroblasts were separated by SDS-PAGE and stained with colloidal Coomassie; the bands α(I) and α(II) (i.e., at the selected molecular mass values) were excised and destained in 0.1% TFA: ACN 1:1 (v/v).
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_12:17:23.409.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Simona Nonnis
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	O5-galactosyl-L-hydroxylysine; O5-glucosylgalactosyl-L-hydroxylysine; monohydroxylated residue; iodoacetic acid derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-28 03:25:24	ID requested
⏵ 1	2025-05-06 12:17:24	announced

10.1172/jci.insight.181570;

Besio R, Garibaldi N, Sala A, Tonelli F, Aresi C, Maffioli E, Casali C, Torriani C, Biggiogera M, Villani S, Rossi A, Tedeschi G, Forlino A, The administration of exogenous HSP47 as a collagen-specific therapeutic approach. JCI Insight, 10(6):(2025) [pubmed]

submitter keyword: Proteomics

nanoLC-MS/MS

Elisa Maffioli
contact affiliation	Department of Veterinary Medicine and Animal Sciences (DIVAS), University of Milano
contact email	elisa.maffioli@unimi.it
lab head
Simona Nonnis
contact affiliation	University of Milan
contact email	simona.nonnis@unimi.it
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD047320
     1. Label: PRIDE project
     2. Name: Administration of recombinant HSP47 as a new therapeutic approach to stimulate collagen secretion and ameliorate ECM in osteogenesis imperfecta