| Project/Area Number |
24790201
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
General anatomy (including Histology/Embryology)
|
|---|
| Research Institution | Juntendo University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2012-04-01 – 2014-03-31
|
| Project Status |
Completed (Fiscal Year 2013)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
|
|---|
| Keywords | リソソーム / 腎虚血再灌流傷害 / カテプシンDノックアウトマウス / オートファジー / 虚血再灌流傷害 / 腎尿細管上皮 / カテプシンD / リソソームプロテアーゼ / 形態学 |
|---|
| Research Abstract |
Ischemia reperfusion (I/R) injury is inevitable in kidney transplantation. Here show roles of lysosomal proteinases in renal I/R injury. For this, we prepared CDflox/-:Cre-Spink3 in which CD is deficient in renal proximal tubular epithelial cells (RPTECs). Even under physiological conditions, CD-deficient PRTECs contain a lamellarly arranged endoplasmic-reticulum (LER), fingerprint profiles, and autophagosomes (AP), although these changes were detected in the RPTECs of wild-type (wt) mice after I/R injury. After I/R, damage in CD-deficient RPTECs was much severer than in wt mice. Moreover, these CD-deficient RPTECs had more increased numbers of AP and LER after I/R and dying cells occupied with these AP and aberrant membrane structures appeared in the lumen of RPT. These results suggest that RPTECs deficient in CD may largely undergo cell death, because of excess of autophagy. Taken together, lysosomal proteinases as well as autophagy was largely involved in IR-induced death of RPTECs.
|
