Dr. Yang, Kai-Chien 's publons link picture

Dr. Yang, Kai-Chien

Joint Appointment Associate Research Fellow
  • 2652-3597 (Lab) (Room No: N717)

  • Organ fibrosis and stromal biology
  • Cardiac regeneration
  • Non-coding RNA biology
  • Ion channel regulation and electrophysiology
  • Cardiac oxidative stress and arrhythmias

Education and Positions:
    • M.D. National Taiwan University
    • Ph.D. Washington University in St. Louis
    • Associate Professor, Department and Graduate Institute of Pharmacology, National Taiwan University
    • Attending physician, Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital

Highlight Detail

Endoplasmic reticulum protein TXNDC5 promotes renal fibrosis by enforcing TGFβ signaling in kidney fibroblasts

Dr. Yang, Kai-Chien
Journal of Clinical Investigation, Jan 19, 2021


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.