Endoplasmic reticulum stress and collagenous formation anomalies in vascular‐type Ehlers–Danlos syndrome via electron microscopy

Vascular‐type Ehlers–Danlos syndrome (vEDS) is an autosomal‐dominant inherited disorder caused by a deficit in collagen III. It results from heterogeneous mutations in the α1 collagen III gene (COL3A1) and is associated with life‐threatening complications, even in younger patients. However, the deta...

Full description

Saved in:
Bibliographic Details
Published in:Journal of dermatology 2021-04, Vol.48 (4), p.481-485
Main Authors: Ishikawa, Satoko, Kosho, Tomoki, Kaminaga, Tomoko, Miyamoto, Manabu, Hamasaki, Yoichiro, Yoshihara, Shigemi, Hayashi, Shujiro, Igawa, Ken
Format: Article
Language:English
Subjects:
Activating transcription factor 6
Cartilage
Cartilage oligomeric matrix protein
Collagen
Collagen (type III)
Collagen Type III - genetics
Dermis
Ehlers-Danlos syndrome
Ehlers-Danlos Syndrome - diagnosis
Ehlers-Danlos Syndrome - genetics
Electron microscopy
Endoplasmic reticulum
Endoplasmic Reticulum Stress
Fibrils
Hereditary diseases
Humans
Infants
Matrix protein
Microscopy
Microscopy, Electron
Mutation
vascular‐type Ehlers–Danlos syndrome
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Vascular‐type Ehlers–Danlos syndrome (vEDS) is an autosomal‐dominant inherited disorder caused by a deficit in collagen III. It results from heterogeneous mutations in the α1 collagen III gene (COL3A1) and is associated with life‐threatening complications, even in younger patients. However, the details of the pathogenesis underlying the COL3A1 mutation causing vEDS remain unclear. Here, we focus on anomalies in collagen fiber size and the endoplasmic reticulum (ER) stress response in patients with vEDS using electron microscopy (EM). We discovered that although the infants did not have vEDS, collagenous formations were similar to their samples in vEDS. Moreover, we examined the expression of activating transcription factor 6 (ATF6) as an ER stress marker and cartilage oligomeric matrix protein (COMP) as a binding partner protein for collagen fibrils in the dermis and COL3A1. The expression levels of ATF6 in the vEDS group were significantly higher than in infants and controls; COMP and COL3A1 levels were significantly lower. The fragile collagen fibrils in vEDS might form as a result of ER stress and that small, newly formed collagen fibrils may appear. This research revealed a novel prospect regarding an issue that has been unclear for a long time, which is the reason for the abnormal sizes of collagenous fibrils in vEDS.
ISSN:0385-2407
1346-8138
DOI:10.1111/1346-8138.15766