- 作者: Chen-Ting Hung, Yi-Wei Tsai, Yu-Shuo Wu, Chih-Fan Yeh & Kai-Chien Yang
- 作者服務機構: 1.Center for Frontier Medicine, National Taiwan University Hospital, Taipei, Taiwan 2.Department and Graduate Institute of Pharmacology, National Taiwan University College of Medicine, No. 1, Sec. 1, Ren-Ai Rd, 1150R, Taipei, 100, Taiwan 3.Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan 4.Division of Cardiology, Department of Internal Medicine and Cardiovascular Center, National Taiwan University Hospital, Taipei, Taiwan 5.Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan 6.Research Center for Developmental Biology & Regenerative Medicine, National Taiwan University, Taipei, Taiwan
- 中文摘要:
- 英文摘要:
Fibrosis-related disorders account for an enormous burden of disease-associated morbidity and mortality world‑
wide. Fibrosis is defned by excessive extracellular matrix deposition at fbrotic foci in the organ tissue following
injury, resulting in abnormal architecture, impaired function and ultimately, organ failure. To date, there lacks efec‑
tive pharmacological therapy to target fbrosis per se, highlighting the urgent need to identify novel drug targets
against organ fbrosis. Recently, we have discovered the critical role of a fbroblasts-enriched endoplasmic reticulum
protein disulfde isomerase (PDI), thioredoxin domain containing 5 (TXNDC5), in cardiac, pulmonary, renal and liver
fbrosis, showing TXNDC5 is required for the activation of fbrogenic transforming growth factor-β signaling cascades
depending on its catalytic activity as a PDI. Moreover, deletion of TXNDC5 in fbroblasts ameliorates organ fbrosis and
preserves organ function by inhibiting myofbroblasts activation, proliferation and extracellular matrix production. In
this review, we detailed the molecular and cellular mechanisms by which TXNDC5 promotes fbrogenesis in various
tissue types and summarized potential therapeutic strategies targeting TXNDC5 to treat organ fbrosis. - 中文關鍵字:
- 英文關鍵字: Organ fbrosis, TXNDC5, Protein disulfde isomerase, Thioredoxin domain, Transforming growth factor-β (TGFβ)