Elucidation of mechanism of renal fibrosis and prognosis in chronic kidney disease by analyzing factors originated from tubular epithelium

• Project/Area Number: 18K16002
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Tokai University
• Principal Investigator: TANAKA Keiko 東海大学, 医学部, 奨励研究員 (80794370)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 慢性腎臓病 / 尿細管間質線維化 / トレフォイルファクター / 尿細管間質性障害 / TFF / 間質線維化 / 予後予測

Outline of Final Research Achievements

Trefoil factor (TFF) is a small peptide that is involved in mucosal protection. TFF3 is widely expressed in multiple tissues including kidney. Previous studies have reported that the urinary TFF3 levels are　significantly increased in patients with chronic kidney disease (CKD). The aim of this study is to elucidate the significance of TFF3 in CKD patients.
The renal TFF3 mRNA was significantly associated with the urinary TFF3 excretion and the tubulointerstitial fibrosis score in patients of IgA nephropathy (IgAN). Immunostaining of the renal biopsy specimen of IgAN patients revealed that TFF3 is located in the renal tubular epithelial cells. The locations were almost the same as those that showed uromodulin positivity. The urinary TFF3 levels were positively correlated with the levels of urinary biomarkers of tubulointerstitial injury in such patients.
TFF3 was associated with renal tubulointerstitial fibrosis, and may be valuable as a prognostic factor in IgAN patients.

Academic Significance and Societal Importance of the Research Achievements

慢性腎臓病の中でも、日本人に多いIgA腎症において、その腎予後は間質障害度や線維化と関連があるとされるが、その機序や予後予測因子は明らかになっていない。今回TFF3が、IgA腎症における間質障害、とくに間質線維化を反映し、尿中TFF3増加がIgA腎症の腎予後予測因子となりうる可能性が示唆された。

Research Products

• [Journal Article] Podocyte autophagy is associated with foot process effacement and proteinuria in patients with minimal change nephrotic syndrome. (2020)
  • Author(s): Ogawa-Akiyama A, Sugiyama H, Kitagawa M, Tanaka K, Kano Y, Mise K, Otaka N, Tanabe K, Morinaga H, Kinomura M, Uchida HA, Wada J.
  • Journal Title: PLoS One. Volume: 15(1) Issue: 1 Pages: 1-15
  • DOI: 10.1371/journal.pone.0228337
  • NAID: 120006862788
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Urine 5MedC, a Marker of DNA Methylation, in the Progression of Chronic Kidney Disease (2019)
  • Author(s): Onishi Akifumi、Sugiyama Hitoshi、Kitagawa Masashi、Yamanari Toshio、Tanaka Keiko、Ogawa-Akiyama Ayu、Kano Yuzuki、Mise Koki、Tanabe Katsuyuki、Morinaga Hiroshi、Kinomura Masaru、Uchida Haruhito A.、Wada Jun
  • Journal Title: Disease Markers Volume: 2019 Pages: 1-10
  • DOI: 10.1155/2019/5432453
  • Peer Reviewed / Open Access
• [Journal Article] Renal expression of trefoil factor 3 mRNA in association with tubulointerstitial fibrosis in IgA nephropathy (2018)
  • Author(s): Tanaka Keiko、Sugiyama Hitoshi、Yamanari Toshio、Mise Koki、Morinaga Hiroshi、Kitagawa Masashi、Onishi Akifumi、Ogawa-Akiyama Ayu、Tanabe Katsuyuki、Eguchi Jun、Ohmoto Yasukazu、Shikata Kenichi、Wada Jun
  • Journal Title: Nephrology Volume: 23 Issue: 9 Pages: 855-862
  • DOI: 10.1111/nep.13444
  • Peer Reviewed / Open Access / Int'l Joint Research