Autophagy and podocytopathy.
Nephrol Dial Transplant
; 38(9): 1931-1939, 2023 08 31.
Article
in En
| MEDLINE
| ID: mdl-36708169
ABSTRACT
Autophagy is a complex process of lysosomal-dependent degradation of unwanted cellular material. In response to endogenous or exogenous stimuli, autophagy is induced and regulated by two kinases the AMP activated kinase and the mammalian target of rapamycin (mTOR). Cells activated by Unc-51-like kinase 1 form a double membrane complex that sequesters the cargo (phagophore) and elongates producing spherical vesicles (autophagosomes). These reach and fuse with lysosomes, which degrade the cargo (autolysosomes). The resulting macromolecules are released back and recycled in the cytosol for reuse. In the podocyte, autophagy is a homeostatic mechanism that contributes to the formation and preservation of the morphological and functional integrity of actin cytoskeleton. Podocytes, fenestrated endothelial cells and glomerular basement membrane compose the glomerular filtration barrier. Podocyte damage may cause dysfunction of the glomerular barrier, proteinuria and glomerulosclerosis in different glomerular diseases and particularly in so-called podocytopathies, namely minimal change disease and focal segmental glomerulosclerosis. Several drugs and molecules may activate autophagic function in murine models. Among them, aldosterone inhibitors, mineralocorticoid inhibitors and vitamin D3 were proven to protect podocyte from injury and reduce proteinuria in clinical studies. However, no clinical trial with autophagy regulators in podocytopathies has been conducted. Caution is needed with other autophagy activators, such as mTOR inhibitors and metformin, because of potential adverse events.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Glomerulosclerosis, Focal Segmental
/
Podocytes
/
Kidney Diseases
Limits:
Animals
/
Humans
Language:
En
Journal:
Nephrol Dial Transplant
Journal subject:
NEFROLOGIA
/
TRANSPLANTE
Year:
2023
Type:
Article
Affiliation country:
Italy