https://scholars.lib.ntu.edu.tw/handle/123456789/630965
標題: | The novel role of ER protein TXNDC5 in the pathogenesis of organ fibrosis: mechanistic insights and therapeutic implications | 作者: | Hung, Chen-Ting Tsai, Yi-Wei Wu, Yu-Shuo CHIH-FAN YEH Yang, Kai-Chien |
關鍵字: | Organ fibrosis; Protein disulfide isomerase; TXNDC5; Thioredoxin domain; Transforming growth factor-β (TGFβ) | 公開日期: | 2-九月-2022 | 出版社: | BMC | 卷: | 29 | 期: | 1 | 起(迄)頁: | 63 | 來源出版物: | Journal of biomedical science | 摘要: | Fibrosis-related disorders account for an enormous burden of disease-associated morbidity and mortality worldwide. Fibrosis is defined by excessive extracellular matrix deposition at fibrotic foci in the organ tissue following injury, resulting in abnormal architecture, impaired function and ultimately, organ failure. To date, there lacks effective pharmacological therapy to target fibrosis per se, highlighting the urgent need to identify novel drug targets against organ fibrosis. Recently, we have discovered the critical role of a fibroblasts-enriched endoplasmic reticulum protein disulfide isomerase (PDI), thioredoxin domain containing 5 (TXNDC5), in cardiac, pulmonary, renal and liver fibrosis, showing TXNDC5 is required for the activation of fibrogenic transforming growth factor-β signaling cascades depending on its catalytic activity as a PDI. Moreover, deletion of TXNDC5 in fibroblasts ameliorates organ fibrosis and preserves organ function by inhibiting myofibroblasts activation, proliferation and extracellular matrix production. In this review, we detailed the molecular and cellular mechanisms by which TXNDC5 promotes fibrogenesis in various tissue types and summarized potential therapeutic strategies targeting TXNDC5 to treat organ fibrosis. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/630965 | ISSN: | 1021-7770 | DOI: | 10.1186/s12929-022-00850-x |
顯示於: | 醫學系 |
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