Breg-IL-10 system as a novel therapeutic target for CKD
| Project/Area Number |
19K08693
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 53040:Nephrology-related
|
|---|
| Research Institution | Kurume University |
|---|
Principal Investigator |
FUKAMI KEI 久留米大学, 医学部, 教授 (80309781)
|
|---|
| Project Period (FY) |
2019-04-01 – 2022-03-31
|
| Project Status |
Completed (Fiscal Year 2021)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | AKI / IL10 / reperfusion / Breg / IL-10 / IRI / 組織修復 / B cell / Diabetic Nephropathy / Re-perfusion injury |
|---|
| Outline of Research at the Start |
糖尿病性腎症進展や急性腎障害から末期腎不全に至る症例は増加の一途を辿っている。これら腎機能低下の主座は、最終共通経路としての細胞浸潤、高度な線維化、尿細管間質障害である。近年様々な腎傷害抑制因子が同定されているが、修復過程を制御する研究はなされていない。B細胞性免疫は腎組織修復に深く関与しているものの、これら腎障害進展における修復過程に制御性B細胞(Breg)-IL-10系がいかに関与し腎保護的に働くかは定かではない。これらが解明されれば、Bregの移入療法が糖尿病性腎症や急性腎障害から末期腎不全への進展を阻止するという新たな腎臓病治療ストラテジーになると考えている。
|
| Outline of Final Research Achievements |
In this study, we examined whether IL-10-expressed Breg is associated with the pathogenesis of AKI-to CKD in re-perfusion-induced AKI model IL-10GFP mice. We found that in this AKI model, IL-10 expression was time-dependently decreased in the glomeruli and increased in the renal medulla by IR. Decrease in IL-10 expression in the glomeruli occurred before the progression to glomerulosclerosis in this AKI model. To identify the existence of Breg in the kidney, we stained with CD19, as a B cell marker, and we found the colocalization of IL-10 and CD19 in the mesangial area of the glomeruli. These expression was also diminished by the IR. These findings suggest that mesangial cells might work as a Breg to inhibit the progression to CKD by IR-induced AKI. Breg in the glomeruli might be an important therapeutic target to prevent the progression of AKI-to-CKD.
|
| Academic Significance and Societal Importance of the Research Achievements |
近年、AKIは様々な状況で生じることが明らかとなっている。特に高齢者においては動脈硬化による腎虚血からAKIを引き起こし、その後CKDへ移行する。その過程において、尿細管障害が腎障碍の首座と考えられてきたが、我々は糸球体の変化に着目し研究を行った。現状ではAKI-to-CKDへの移行を阻止するための治療法は確立されていない。今回我々は、世界で初めてメサンギウム細胞がBregとして機能していることを見出した。今後はメサンギウム細胞のBregとしての機能解析と治療応用を考えており、新規治療ターゲットとして研究を発展させることは、社会的にも大変意義があることと考える。
|
Report
(4 results)
Research Products
(21 results)
-
[Journal Article] Effect of tolvaptan on renal involvement in patients with autosomal dominant polycystic kidney disease according to different gene mutations.2021
Author(s)
Moriyama T, Nakayama Y, Soejima M, Yokota Y, Ota K, Ito S, Kodama G, Nakamura N, Kurokawa Y, Yano J, Ueda U, Takamiya Y, Kaida Y, Hazama T, Shibata R, Koda Y, Fukami K.
-
Journal Title
Clin Exp Nephrol.
Volume: 25
Issue: 3
Pages: 251-260
DOI
Related Report
Peer Reviewed / Open Access
-
-
[Journal Article] Safety and efficacy of single-needle leukocyte apheresis (LCAP) for treatment of ulcerative colitis2020
Author(s)
Shindo Y, Mitsuyama K, Yamasaki H, Imai T, Yoshioka S, Kuwaki K, Yamauchi R, Yoshimura T, Araki T, Morita M, Tsuruta K, Yamasaki S, Fukami K, Torimura T
-
Journal Title
Therapeutic Apheresis and Dialysis
Volume: 24
Issue: 5
Pages: 503-510
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
[Journal Article] Effect of switching from cinacalcet to etelcalcetide on secondary hyperparathyroidism in patients undergoing hemodialysis: an ESCORT trial.2020
Author(s)
Kurokawa Y, Kaida Y, Hazama T, Nakayama Y, Otome T, Shibata R, Ito S, Kodama G, Nakamura N, Kambe T, Moriyama T, Nagata A, Minami A, Ando R, Wada Y, Sugiyama M, Usui M, Chiba M, Moriyama A, Ohara A, Miyazaki H, Kakuma T, Fukami K.
-
Journal Title
Renal Replacement Therapy 6:64, 2020
Volume: 6
Pages: 64-64
Related Report
Peer Reviewed / Open Access
-
-
-
-
[Journal Article] Single Needle Granulocyte and Monocyte Apheresis for Ulcerative Colitis: A Retrospective Safety Analysis2019
Author(s)
Imai T, Yamasaki H, Mitsuyama K, Yamaga O, Sugihara G, Kaida Y, Shibata R, Hazama T, Yoshioka S, Torimura T, Fukami K, Yamashita N.
-
Journal Title
The Kurume Medical Journal
Volume: 66
Issue: 1
Pages: 1-7
DOI
NAID
ISSN
0023-5679, 1881-2090
Year and Date
2019-03-31
Related Report
Peer Reviewed / Open Access
-
-
[Journal Article] Effectiveness of cryofiltration and mizoribine combination with oral steroid therapy in a patient with membranoproliferative glomerulonephritis due to essential cryoglobulinemia.2019
Author(s)
Kurokawa Y, Koike K, Kaida Y, Ito S, Chiba H, Urae K, Moriyama T, Nakamura N, Imai T, Shibata R, Hazama T, Wakasugi D, Okuda S, Fukami K
-
Journal Title
CEN Case Rep
Volume: 8
Issue: 3
Pages: 205-211
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Effectiveness of immunosuppressive therapy for nephrotic syndrome in a patient with late-onset Fabry disease: a case report and literature review.2019
Author(s)
Fujisawa H, Nakayama Y, Nakao S, Yamamoto R, Kurokawa Y, Nakamura N, Nagata A, Tsukimura T, Togawa T, Sakuraba H, Fukami K.
-
Journal Title
BMC Nephrol
Volume: 20
Issue: 1
Pages: 469-469
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
