Dataset Information

Uncoupling TGFβ1 signalling from collagen protein synthesis in Dupuytren’s disease: metabolic labelling and proteomics analysis of Dupuytren’s cord, nodule and normal palmar fascia controls (C4PR_LIV)

ABSTRACT: Dupuytren’s disease is a fibroproliferative disorder of the palmer fascia characterized by flexion contractures in the hand. Dupuytren’s can be treated surgically but disease recurrence rates are high, potentially due to a continual production of matrisomal proteins. Metabolic labelling and proteomics were used to determine the differences in the new synthesis and composition of matrisomal proteins between Dupuytren’s tissue and normal palmar fascia. Dupuytren’s tissue actively synthesised type I collagen, fibronectin, matrix metalloproteinases-2 and -3 (MMP2, MMP3) and Tissue Inhibitor of Metalloproteinases 2 (TIMP2). Both tissues actively synthesized Insulin-Like Growth Factor Binding Protein 7 (IGFBP7). Label-free analysis implicated the TGFβ pathway in the matrisomal profile of Dupuytren’s tissue.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Fascia

DISEASE(S): Plantar Fascial Fibromatosis

SUBMITTER: Philip Brownridge

LAB HEAD: Dr Elizabeth Laird

PROVIDER: PXD069194 | Pride | 2026-03-16

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	DS_120917_48M_pos_CT.mgf	Mgf
	DS_120917_48M_pos_CT.mzid	Mzid
	DS_120917_48M_pos_CT.raw	Raw
	DS_120917_49M_pos_cord.mgf	Mgf
	DS_120917_49M_pos_cord.mzid	Mzid

Items per page:

1 - 5 of 113

Publications

Uncoupling TGFβ1 signalling from collagen protein synthesis in Dupuytren's disease.

Cooper Gabriella G Gumbs Jade A JA Alkharabsheh Sahem S Lee Katie J KJ Carter Alan A Coleman Hannah H O'Heneghan-Yates Niamh S NS Ijaz Rama R Beamish Emma E Menezes Lisa A LA Liloglou Triantafillos T Clegg Peter D PD Canty-Laird Elizabeth G EG

The Journal of pathology 20260126

Dupuytren's disease is a fibroproliferative disorder of the palmer fascia (PF) characterised by flexion contractures in the hand. Dupuytren's disease can be treated surgically, but disease recurrence rates are high, potentially due to continual production of matrisomal proteins. Here, metabolic labelling and proteomics identified differences in the new synthesis and composition of matrisomal proteins between Dupuytren's tissue and normal PF. Dupuytren's tissue actively synthesised type I collage ...[more]

PMID: 41588641

Similar Datasets

Project description:Glioblastoma (GBM) is the most common and malignant primary brain tumor. The extracellular matrix (ECM), also known as the matrisome, helps determine glioma invasion, adhesion, and growth. Little attention, however, has been paid to glycosylation of the ECM components that constitute the majority of glycosylated protein mass and presumed biological properties. To acquire a comprehensive understanding of the biological functions of the matrisome and its components, including proteoglycans and glycosaminoglycans (GAGs), in GBM tumorigenesis, and to identify potential biomarker candidates, we studied the alterations of GAGs, including heparan sulfate (HS) and chondroitin sulfate (CS), the core proteins of proteoglycans, and other glycosylated matrisomal proteins in GBM subtypes vs. control human brain tissue samples. We scrutinized the proteomics data to acquire in-depth site-specific glycoproteomic profiles of the GBM subtypes that will assist in identifying specific glycosylation changes in GBM. We observed an increase in CS 6-O sulfation and a decrease in HS 6-O sulfation, accompanied by an increase in unsulfated CS and HS disaccharides in GBM vs. control samples. Several core matrisome proteins, including proteoglycans (decorin, biglycan, agrin, prolargin, glypican-1, CSPG4), tenascin, fibronectin, hyaluronan link protein 1 and 2, laminins, and collagens, were differentially regulated in GBM vs. controls. Interestingly, a higher degree of collagen hydroxyprolination was also observed for GBM vs. controls. Further, two proteoglycans, CSPG4 and agrin, were significantly lower, about 6–fold for IDH-mutant compared to the WT GBM samples. Differential regulation of O-glycopeptides for proteoglycans, including brevican, neurocan, and versican, was observed for GBM subtypes vs. controls. Moreover, an increase in levels of glycosyltransferase and glycosidase enzymes was observed for GBM when compared to control samples. We also report distinct protein, peptide, and glycopeptide features for GBM subtypes comparisons. Taken together, our study informs understanding of the alterations to key matrisomal molecules that occur during GBM development.

Project description:Equine odontoclastic tooth resorption and hypercementosis (EOTRH) is a relatively recently described dental disorder, commonly found in horses above the age of 15 years old (Carsten Staszyk et al. 2008). The disease was first categorised as EOTRH in 2008, following the identification of clinical cases involving severe resorptive lesions and cementomas forming on the lower portion of equine incisors (Kreutzer et al. 2007) (Baratt 2007). The two main disease indicators are resorptive lesions caused by odontoclasts and hypercementosis, characterised by reparative/irregular cementum deposition, forming bulbous-like features (Schätzle, Tanner, and Bosshardt 2005). Horses with severe EOTRH often present dysphagia, pain whilst eating and behavioral changes, which may lead to further unrelated complications (Earley and Rawlinson 2013). Some suggested that Warmbloods and Thoroughbreds are more commonly diagnosed (Sykora et al, 2014; Smedley et al, 2015; Lorello et al, 2016; Earley et al, 2017), although others state there are no appar¬ent breed associations (James, 2022; Tretow et al, 2023). Furthermore, in a limited group of Icelandic horses, a diagnosis was established in 72.2% of cases (Tretow, Hain, and Bienert-Zeit 2023). While radiography is the primary diagnostic method for EOTRH after clinical examination, recent studies have indicated that this approach may lack sensitivity for early disease detection, potentially impeding treatment if the condition has advanced significantly (Albers, Bienert-Zeit, and Staszyk 2022). A comparable ailment observed in cats is Feline Odontoclastic Resorptive Lesions (FORL). In this species there was a prevalence of 29% , and similar to EOTRH, it exhibited an elevated risk associated with age (Gorrel 2014). The underlying causes of EOTRH are not yet fully understood with many potential factors considered, including age, sex, breed, diet and environment (Pearson et al. 2013). One of the first theories suggest a sequence of events beginning with periodontal inflammation leading to resorptive lesions and subsequent cementum production (Carsten Staszyk et al. 2008). Other studies found gram-negative bacteria (Treponema, Tannerella) were more commonly identified in the gingival crevicular fluid of diseased horses, highlighting the potential importance of the oral microbiome in disease aetiology (Sykora et al. 2013). Current treatment involves extraction of affected teeth. However there is an increased likelihood of neighboring teeth developing EOTRH (Rahmani et al. 2019). Presently there are no reported disease modifying treatments available to treat EOTRH and symptom management and pain reduction are the current gold standard approaches (Foster 2013). Whilst the cementum of teeth is the most effected dental tissue other types of dental tissues include dentine, enamel, pulp and the periodontium. The latter consists of cementum, periodontal ligament and alveolar bone. Compositionally cementum is similar to bone with 55% organic material and 45% inorganic hydroxyapatite (Tziafas 2005). It covers the entire length of equine teeth, potentially explaining the hyperactivity of cementum-producing cells (cementoblasts) in EOTRH [C. Staszyk, Suske, and Pöschke (2015)](Bosshardt 2005). Coronal cementum acts as a support to enamel, whilst cementum nearer to the roots is primarily an interface between tooth and the periodontal ligament (PDL). Finally a third type of cementum is present within the infundibulum near the coronal surface of the tooth. Irregular cementum has been shown to be deposited during EOTRH at both resorbed and non-resorbed surfaces along the tooth-PDL interface. Proteomic tools have been utilised to analyse clinical samples in both normal and disease-specific states. Specifically in dental tissues proteomics has been used to map proteomes of enamel, dentin, cementum and pulp in human teeth [Green et al. (2019)](Widbiller et al. 2019)[Giovani et al. (2020)](Eckhardt et al. 2014). As well as this human dental diseases, such as gingivitis, caries and periodontal disease have all been investigated with a similar approach [Gonçalves et al. (2011)](Wang et al. 2018)(Hartenbach et al. 2020). There have been no studies performed to identify potential pathological distinctions between the cementum tissues from healthy horses and those with EOTRH. We hypothesised that global protein changes in horses with and without EOTRH would increase the understanding of underlying pathways and disease mechanisms enabling insight into aetiologies. In addition, by understanding the pathophysiological mechanisms related to EOTRH this could provide treatment targets to delay or prevent disease progression. To investigate protein profiles we used unbiased label-free mass spectrometry-based proteomics.