Decreased Podocyte Vesicle Transcytosis and Albuminuria in APC C-Terminal Deficiency Mice with Puromycin-Induced
Saaya Hatakeyama1, Akihiro Tojo1, Hiroshi Satonaka1
1Department of Nephrology & Hypertension, Dokkyo Medical University, Tochigi 321-0293, Japan.
Abstract:
In minimal change nephrotic syndrome, podocyte vesicle transport is enhanced. Adenomatous polyposis coli (APC) anchors microtubules to cell membranes and plays an important role in vesicle transport. To clarify the role of APC in vesicle transport in podocytes, nephrotic syndrome was induced by puromycin amino nucleoside (PAN) injection in mice expressing APC1638T lacking the C-terminal of microtubule-binding site (APC1638T mouse); this was examined in renal tissue changes. The kidney size and glomerular area of APC1638T mice were reduced (p = 0.014); however, the number of podocytes was same between wild-type (WT) mice and APC1638T mice. The ultrastructure of podocyte foot process was normal by electron microscopy. When nephrotic syndrome was induced, the kidneys of WT+PAN mice became swollen with many hyaline casts, whereas these changes were inhibited in the kidneys of APC1638T+PAN mice. Electron microscopy showed foot process effacement in both groups; however, APC1638T+PAN mice had fewer vesicles in the basal area of podocytes than WT+PAN mice. Cytoplasmic dynein-1, a motor protein for vesicle transport, and α-tubulin were significantly reduced in APC1638T+PAN mice associated with suppressed urinary albumin excretion compared to WT+PAN mice. In conclusion, APC1638T mice showed reduced albuminuria associated with suppressed podocyte vesicle transport when minimal change nephrotic syndrome was induced.
Insights
Adenomatous polyposis coli (APC) is crucial for vesicle transport in podocytes. Mice with a modified APC protein showed reduced albuminuria and suppressed vesicle transport during nephrotic syndrome.
Area of Science:
- Nephrology
- Cell Biology
- Molecular Medicine
Background:
- Minimal change nephrotic syndrome is characterized by enhanced podocyte vesicle transport.
- Adenomatous polyposis coli (APC) is vital for anchoring microtubules and facilitating vesicle transport.
Purpose of the Study:
- To investigate the role of APC in podocyte vesicle transport during nephrotic syndrome.
- To examine renal tissue changes in mice with a modified APC protein (APC1638T) lacking its C-terminal microtubule-binding site.
Main Methods:
- Nephrotic syndrome was induced in APC1638T and wild-type (WT) mice using puromycin amino nucleoside (PAN).
- Kidney size, glomerular area, podocyte number, and ultrastructure were analyzed.
- Electron microscopy assessed podocyte foot process and vesicle presence.
- Levels of cytoplasmic dynein-1 and α-tubulin were quantified.
Main Results:
- APC1638T mice exhibited reduced kidney size and glomerular area compared to WT mice.
- PAN-induced kidney swelling and hyaline casts were inhibited in APC1638T+PAN mice.
- APC1638T+PAN mice showed reduced podocyte basal vesicles, cytoplasmic dynein-1, and α-tubulin.
- Reduced urinary albumin excretion was observed in APC1638T+PAN mice.
Conclusions:
- The modified APC protein (APC1638T) suppressed podocyte vesicle transport.
- APC1638T mice demonstrated reduced albuminuria in a minimal change nephrotic syndrome model.
- APC plays a significant role in regulating vesicle transport in podocytes.
