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ResearchIn-Press PreviewCell biologyNephrology Free access | 10.1172/JCI143645
1Department and Graduate Institute of Pharmacology, National Taiwan University College of Medicine, Taipei City, Taiwan
2Department of Biomedical Engineering, National Taiwan University College of Medicine and College of Engineering, Taipei City, Taiwan
3Department of Dermatology, National Taiwan University Hospital and College of Medicine, Taipei City, Taiwan
4Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan
5Department and Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei City, Taiwan
Find articles by Chen, Y. in: JCI | PubMed | Google Scholar
1Department and Graduate Institute of Pharmacology, National Taiwan University College of Medicine, Taipei City, Taiwan
2Department of Biomedical Engineering, National Taiwan University College of Medicine and College of Engineering, Taipei City, Taiwan
3Department of Dermatology, National Taiwan University Hospital and College of Medicine, Taipei City, Taiwan
4Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan
5Department and Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei City, Taiwan
Find articles by Jhao, P. in: JCI | PubMed | Google Scholar
1Department and Graduate Institute of Pharmacology, National Taiwan University College of Medicine, Taipei City, Taiwan
2Department of Biomedical Engineering, National Taiwan University College of Medicine and College of Engineering, Taipei City, Taiwan
3Department of Dermatology, National Taiwan University Hospital and College of Medicine, Taipei City, Taiwan
4Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan
5Department and Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei City, Taiwan
Find articles by Hung, C. in: JCI | PubMed | Google Scholar
1Department and Graduate Institute of Pharmacology, National Taiwan University College of Medicine, Taipei City, Taiwan
2Department of Biomedical Engineering, National Taiwan University College of Medicine and College of Engineering, Taipei City, Taiwan
3Department of Dermatology, National Taiwan University Hospital and College of Medicine, Taipei City, Taiwan
4Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan
5Department and Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei City, Taiwan
Find articles by Wu, Y. in: JCI | PubMed | Google Scholar
1Department and Graduate Institute of Pharmacology, National Taiwan University College of Medicine, Taipei City, Taiwan
2Department of Biomedical Engineering, National Taiwan University College of Medicine and College of Engineering, Taipei City, Taiwan
3Department of Dermatology, National Taiwan University Hospital and College of Medicine, Taipei City, Taiwan
4Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan
5Department and Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei City, Taiwan
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Lin, S.
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1Department and Graduate Institute of Pharmacology, National Taiwan University College of Medicine, Taipei City, Taiwan
2Department of Biomedical Engineering, National Taiwan University College of Medicine and College of Engineering, Taipei City, Taiwan
3Department of Dermatology, National Taiwan University Hospital and College of Medicine, Taipei City, Taiwan
4Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan
5Department and Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei City, Taiwan
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Chiang, W.
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1Department and Graduate Institute of Pharmacology, National Taiwan University College of Medicine, Taipei City, Taiwan
2Department of Biomedical Engineering, National Taiwan University College of Medicine and College of Engineering, Taipei City, Taiwan
3Department of Dermatology, National Taiwan University Hospital and College of Medicine, Taipei City, Taiwan
4Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan
5Department and Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei City, Taiwan
Find articles by
Lin, S.
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1Department and Graduate Institute of Pharmacology, National Taiwan University College of Medicine, Taipei City, Taiwan
2Department of Biomedical Engineering, National Taiwan University College of Medicine and College of Engineering, Taipei City, Taiwan
3Department of Dermatology, National Taiwan University Hospital and College of Medicine, Taipei City, Taiwan
4Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan
5Department and Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei City, Taiwan
Find articles by
Yang, K.
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Published January 19, 2021 - More info
Renal fibrosis, a common pathological manifestation of virtually all types of chronic kidney diseases (CKD), often results in diffuse kidney scarring and predisposes to end-stage renal disease. Currently, there is no effective therapy against renal fibrosis. Recently, our laboratory identified an ER-resident protein, thioredoxin domain containing 5 (TXNDC5), as a critical mediator of cardiac fibrosis. Transcriptome analyses of renal biopsy specimens from CKD patients revealed marked TXNDC5 upregulation in fibrotic kidneys, suggesting a potential role of TXNDC5 in renal fibrosis. Employing multiple fluorescent reporter mouse lines, we showed that TXNDC5 was specifically upregulated in collagen-secreting fibroblasts in fibrotic mouse kidneys. In addition, we showed that TXNDC5 was required for TGFβ1-induced fibrogenic responses in human kidney fibroblasts (HKF), whereas TXNDC5 over-expression was sufficient to promote HKF activation, proliferation and collagen production. Mechanistically, we showed that TXNDC5, transcriptionally controlled by ATF6-dependent ER stress pathway, mediates its pro-fibrogenic effects by enforcing TGFβ signaling activity through post-translational stabilization and upregulation of type I TGFβ receptor in kidney fibroblasts. Using a tamoxifen-inducible, fibroblast-specific Txndc5 knockout mouse line, we demonstrated that deletion of Txndc5 in kidney fibroblasts mitigated the progression of established kidney fibrosis, suggesting the therapeutic potential of TXNDC5 targeting for renal fibrosis and CKD.