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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 蔡沛學 | zh_TW |
| dc.contributor.advisor | PEI-SHIUE TSAI | en |
| dc.contributor.author | 陳葉子 | zh_TW |
| dc.contributor.author | Chanakan Arprayoon | en |
| dc.date.accessioned | 2024-02-26T16:27:13Z | - |
| dc.date.available | 2024-04-10 | - |
| dc.date.copyright | 2024-02-26 | - |
| dc.date.issued | 2022 | - |
| dc.date.submitted | 2002-01-01 | - |
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Shih, Y.C., et al., Endoplasmic Reticulum Protein TXNDC5 Augments Myocardial Fibrosis by Facilitating Extracellular Matrix Protein Folding and Redox-Sensitive Cardiac Fibroblast Activation. Circ Res, 2018. 122(8): p. 1052-1068. 43. Lee, T.-H., et al., Fibroblast-enriched endoplasmic reticulum protein TXNDC5 promotes pulmonary fibrosis by augmenting TGFβ signaling through TGFBR1 stabilization. Nature Communications, 2020. 11(1): p. 4254. 44. Chen, Y.T., et al., Endoplasmic reticulum protein TXNDC5 promotes renal fibrosis by enforcing TGF-β signaling in kidney fibroblasts. J Clin Invest, 2021. 131(5). 45. Chen, X., et al., Inhibition of ER stress by targeting the IRE1α–TXNDC5 pathway alleviates crystalline silica-induced pulmonary fibrosis. International Immunopharmacology, 2021. 95: p. 107519. 46. Hung, C.T., et al., Targeting ER protein TXNDC5 in hepatic stellate cell mitigates liver fibrosis by repressing non-canonical TGFβ signalling. Gut, 2021. 47. Kyrylkova, K., et al., Detection of apoptosis by TUNEL assay. Methods Mol Biol, 2012. 887: p. 41-7. 48. Mueller, S., et al., Cell-cycle progression and response of germ cell tumors to cisplatin in vitro. Int J Oncol, 2006. 29(2): p. 471-9. 49. Roelofs, R.I., et al., Peripheral sensory neuropathy and cisplatin chemotherapy. Neurology, 1984. 34(7): p. 934-8. 50. Callejo, A., et al., Cisplatin-Induced Ototoxicity: Effects, Mechanisms and Protection Strategies. Toxics, 2015. 3(3): p. 268-293. 51. Cherry, S.M., P.A. Hunt, and T.J. Hassold, Cisplatin disrupts mammalian spermatogenesis, but does not affect recombination or chromosome segregation. Mutat Res, 2004. 564(2): p. 115-28. 52. Shoorei, H., et al., The ameliorative effect of carvacrol on oxidative stress and germ cell apoptosis in testicular tissue of adult diabetic rats. Biomedicine & Pharmacotherapy, 2019. 111: p. 568-578. 53. Aldemir, M., et al., Evaluation of the protective effect of quercetin against cisplatin-induced renal and testis tissue damage and sperm parameters in rats. Andrologia, 2014. 46(10): p. 1089-97. 54. Hinz, B., et al., Recent developments in myofibroblast biology: paradigms for connective tissue remodeling. Am J Pathol, 2012. 180(4): p. 1340-55. 55. Michalik, M., et al., Fibroblast-to-myofibroblast transition in bronchial asthma. Cell Mol Life Sci, 2018. 75(21): p. 3943-3961. 56. Santiago, J.J., et al., Cardiac fibroblast to myofibroblast differentiation in vivo and in vitro: expression of focal adhesion components in neonatal and adult rat ventricular myofibroblasts. Dev Dyn, 2010. 239(6): p. 1573-84. 57. Higashiyama, R., et al., Differential Contribution of Dermal Resident and Bone Marrow–Derived Cells to Collagen Production during Wound Healing and Fibrogenesis in Mice. Journal of Investigative Dermatology, 2011. 131(2): p. 529-536. 58. Chen, Y.-T., et al., Lineage Tracing Reveals Distinctive Fates for Mesothelial Cells and Submesothelial Fibroblasts during Peritoneal Injury. Journal of the American Society of Nephrology, 2014. 25(12): p. 2847-2858. 59. Klingberg, F., B. Hinz, and E.S. White, The myofibroblast matrix: implications for tissue repair and fibrosis. J Pathol, 2013. 229(2): p. 298-309. 60. Ruijter, J.M., et al., Removal of between-run variation in a multi-plate qPCR experiment. Biomolecular Detection and Quantification, 2015. 5: p. 10-14. 61. Gong, D., et al., TGFβ signaling plays a critical role in promoting alternative macrophage activation. BMC Immunology, 2012. 13(1): p. 31. 62. Araya, J., et al., Insufficient autophagy in idiopathic pulmonary fibrosis. American Journal of Physiology-Lung Cellular and Molecular Physiology, 2013. 304(1): p. L56-L69. 63. Ghavami, S., et al., Autophagy and the unfolded protein response promote profibrotic effects of TGF-β(1) in human lung fibroblasts. 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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/91919 | - |
| dc.description.abstract | Cisplatin 為常見用於治療不同類型腫瘤之化療藥物。雖其治療效果佳，但治療過程中產生的過量活性含氧物質對於生殖系統，尤其是睪丸會產生嚴重且不可逆之副作用。Cisplatin 造成的副作用包含睪丸組織的損傷，生殖細胞的凋亡，以及生精小管間隙過度細胞外基質的累積。先前研究指出 thioredoxin domain containing 5 (TXNDC5) 為內質網中的雙硫異構酶，與許多器官的纖維化相關，其中包含 cisplatin 所導致的睪丸纖維化 。本篇研究顯示，cisplatin的介入對於生精細胞造成嚴重損傷，睪丸中的TXNDC5 與其他與纖維化相關的蛋白質和基因表現如TGFβ-1、COL1A1 及αSMA都有顯著性的上升。小鼠在剔除TXNDC5 後，發現減緩cisplatin所造成的睪丸損傷，也保留較多生精細胞層。在TXNDC5基因剔除小鼠中，睪丸內的活性含氧物質含量顯著降低，也間接導致細胞凋亡的比例減少。我們結果指出TXNDC5 基因剔除有助於減輕cisplatin所導致的睪丸損傷，並減少與纖維化相關基因與蛋白質表現。調控TXNDC5的表現與功能可能對於改善化學療法導致的睪丸損傷與纖維化有潛在的影響力，並有助接受化療的病人降低不孕症狀和改善其生殖能力。 | zh_TW |
| dc.description.abstract | Cisplatin is the common chemotherapy drug used to treat various kinds of tumors. Even though cisplatin is effective, the side effect on reproductive organs due to excessive production of reactive oxygen species, especially in testis, is severe and irreversible. Side effects of cisplatin in testis were shown in severe testicular damage, including germ cell apoptosis, and excessive accumulation of extracellular matrix (ECM) in the interstitial area of the testis which resulted in fibrosis. Recently, one ER protein disulfide isomerase, thioredoxin domain containing 5 (TXNDC5), was discovered to be involved in the progression of fibrosis in many organs, including in the testis induced by cisplatin. This study demonstrated that after cisplatin administration, spermatogenic cells were significantly destroyed, TXNDC5 and other fibrosis-related protein and gene expression, including TGFβ-1, COL1A1, and αSMA were upregulated. Deletion of TXNDC5 showed the mitigating effect of cisplatin-induced testicular damage by preserving more spermatogenic cells layer. The knockdown mice showed decreased fibrotic protein and gene expression and reduced ECM accumulation in testicular tissue. Furthermore, testicular ROS production from the cisplatin administration was decreased in TXNDC5 knockdown mice with a reduced percentage of cell apoptosis. Our results demonstrate that TXNDC5 is likely to play an important role in cisplatin-induced testicular damages as gene knockdown of TXNDC5 showed reduced testicular damages and down-regulation on the expression of fibrosis-related genes. Targeting TXNDC5 could be a novel therapeutic approach to alleviate the severity of chemotherapy-induced testicular damage and thereby recover the effect of male infertility and reproduction outcomes in chemotherapy-receiving cancer patients. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2024-02-26T16:27:13Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2024-02-26T16:27:13Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 口試委員會審定書…………………………………….………………………i 致謝…….………………………………………...…………………………...ii 中文摘要..…………………..…………………………………......………... iii Abstract…...……………………………………………...……………...…...iv Content.………….……………………………………………………………v List of figures…..……………………………………………...…......……...vii List of tables ………………………………………………………...……….ix CHAPTER 1 Introduction …………………………………………………..…..………….1 Testis ……………………………………………………...……....1 Anatomy of the testis ………………………………………...…....1 1.1.1 interstitial compartment ……………………...…….………...2 1.1.2 Tubular compartment …………………………….…………..2 1.1.3. BTB………………………….…………………....…………4 1.2 Cisplatin ………………………………….………………....…........5 1.2.1 Cisplatin basic information ……………………………..….5 1.2.2 Side effects of cisplatin …………………………………….5 1.2.3 Side effect of cisplatin on testis………………………….…6 1.3 Thioredoxin domain-containing protein 5 (TXNDC5) …………….8 1.4 the scope of the study…………………………………….……...….9 CHAPTER 2 Material and methods……………………………….….......10 2.1 Drug, chemical, reagent, and antibodies………………………......10 2.2 Generation of 〖Txndc5〗^(-/-)mice …………………………………....10 2.3 Cisplatin-induced testicular fibrosis mouse model …………...…...11 2.4 Sample collection ………………………………...……………….13 2.5 Histological evaluation of testicular damage. …………………....13 2.6 Indirect immunofluorescent (IFA) staining …………...….………14 2.7 Immunoblot analysis ………………………………….………..…15 2.8 RNA extraction and qRT-PCR …………………………………...16 2.9 Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNNEL) assay ………………………………………18 2.10 Malondialdehyde (MDA) assay ……………………………….…19 2.11 Statistic analysis ………………………………………………....19 2.12 figure creation ……………………………………………..……..19 CHAPTER 3 Results ………………………………….……………………20 3.1 Body weights were decreased significantly after cisplatin administration ………………………………………………...………20 3.2 Cisplatin led to testicular damage and accumulation of extracellular matrix (ECM) ……………………………………………………………..…...21 3.3 TXNDC5 gene and protein expressions were significantly upregulated in the testes of cisplatin-injured animals ………………...23 3.4 TXNDC5 and collagen1A1 protein expressions were upregulated after cisplatin injection ………………………………...……………...25 3.5 Knockdown of Txndc5 attenuated testicular damage from cisplatin injury…………………………………………………………………..27 3.6 The effects of Txndc5 deletion on the gene and protein expressions of fibrosis markers…………………………………………………...30 3.7 TXNDC5 knockdown augmented lipid peroxidation……………..35 3.8 TXNDC5 knockdown prevented cisplatin-induced cellular apoptosis in the testis…………………………………………….………………36 CHAPTER 4 Discussion……………………………………………………39 Reference …………………………………………………………………....47 | - |
| dc.language.iso | en | - |
| dc.title | 探討含硫氧還原蛋白結構域的5號蛋白質（TXNDC5) 於順鉑藥物誘發之睪丸損傷化中所扮演的角色 | zh_TW |
| dc.title | Investigate the role of thioredoxin domain-containing protein 5 (TXNDC5) in cisplatin-induced testicular damage | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 110-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 張惠雯;張晏禎 | zh_TW |
| dc.contributor.oralexamcommittee | HUI-WEN CHANG;Yen-Chen Chang | en |
| dc.subject.keyword | cisplatin,TXNDC5,睪丸損傷化,活性含氧物,內質網蛋白質, | zh_TW |
| dc.subject.keyword | cisplatin,TXNDC5,testicular damage,ROS,ER protein, | en |
| dc.relation.page | 50 | - |
| dc.identifier.doi | 10.6342/NTU202201862 | - |
| dc.rights.note | 同意授權(限校園內公開) | - |
| dc.date.accepted | 2022-08-11 | - |
| dc.contributor.author-college | 生物資源暨農學院 | - |
| dc.contributor.author-dept | 獸醫學系 | - |
| dc.date.embargo-lift | 2025-08-01 | - |
| 顯示於系所單位： | 獸醫學系 | |
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