Endoplasmic reticulum protein TXNDC5 modulates thyroid eye disease TGF-β1-induced myofibroblast transdifferentiation.

IF 2 Q2 OPHTHALMOLOGY BMJ Open Ophthalmology Pub Date : 2024-12-25 DOI:10.1136/bmjophth-2024-001693
Hsun-I Chiu, Shi-Bei Wu, Albert Y Wu, Chieh-Chih Tsai
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引用次数: 0

Abstract

Aim: There remain limited therapies to treat thyroid eye disease (TED) orbital fibrosis, highlighting the urgency to develop novel targets. Transforming growth factor-β1 (TGF-β1)-induced myofibroblast transdifferentiation from orbital fibroblasts are important pathogenetic factor of TED. Endoplasmic reticulum (ER) stress may play a role in TED pathogenesis since it has been linked to liver, kidney, heart and lung fibrotic remodelling. We would evaluate the role of thioredoxin domain containing 5 (TXNDC5), a fibroblast-enriched ER protein, in TGF-β1-induced myofibroblast transdifferentiation from TED orbital fibroblasts.

Methods: Orbital fibroblasts from patients with TED were treated with TGF-β1 to investigate ER stress-relative gene expression especially for TXNDC5. To determine if TXNDC5 is involved in TGF-β1-induced fibrosis, we transfected TED orbital fibroblasts by lentivirus with a small hairpin RNA of pLKO-TXNDC5 gene (shTXNDC5) to knockdown TXNDC5 protein expression levels. After transfection of shTXNDC5 in TED orbital fibroblast followed by TGF-β1 treatment, we analysed TGF-β1-induced fibrosis protein expression.

Results: We measured increased TXNDC5 gene and protein expression in primary TED orbital fibroblasts. TXNDC5 protein levels were increased in TED orbital fibroblasts under TGF-β1 stimulation (2.5, 5, 10 and 20 ng/mL). Moreover, TXNDC5 knockdown of attenuated TGFβ1 (5 ng/mL)-induced myofibroblast transdifferentiation and extracellular matrix protein upregulation whereas increasing TXNDC5 expression by a recombinant protein of TXNDC5 (rhTXNDC5) addition increased alpha smooth muscle actin, fibronectin and connective tissue growth factor protein expression.

Conclusion: In conclusion, targeting TXNDC5 may be a novel therapeutic approach against TGF-β1-induced myofibroblast transdifferentiation in TED orbital fibroblasts.

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来源期刊
BMJ Open Ophthalmology
BMJ Open Ophthalmology OPHTHALMOLOGY-
CiteScore
3.40
自引率
4.20%
发文量
104
审稿时长
20 weeks
期刊最新文献
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