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Published on: January 31, 2025
VIP17/MAL expression modulates epithelial cyst formation and ciliogenesis.
Vinita Takiar1, Kavita Mistry, Monica Carmosino
1Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, Connecticut 06520-8026, USA.
Vesicle integral protein of 17 kDa (VIP17/MAL) overexpression causes abnormal kidney cyst and primary cilium development. This suggests VIP17/MAL may drive renal cystogenesis through ciliary defects.
Area of Science:
- Cell Biology
- Renal Physiology
- Molecular Medicine
Background:
- Epithelial cell polarization is crucial for kidney function and can be disrupted in renal cystic diseases.
- Vesicle integral protein of 17 kDa (VIP17/MAL) is implicated in apical vesicle transport and its overexpression is linked to renal cystogenesis.
- Primary cilia defects are a known cause of renal cyst development.
Purpose of the Study:
- To investigate the role of VIP17/MAL in renal cystogenesis and ciliogenesis.
- To analyze the effects of VIP17/MAL overexpression on epithelial cell polarization and ciliary morphology.
- To determine if VIP17/MAL-induced cystogenesis is associated with ciliary dysfunction.
Main Methods:
- Utilized Madin-Darby canine kidney (MDCK) epithelial cells in 2D and 3D cyst cultures to study VIP17/MAL effects.
- Examined cell polarization using apical and basolateral markers.
- Assessed primary ciliary morphology and abundance via immunofluorescence in cell cultures and kidney sections from VIP17/MAL transgenic mice.
Main Results:
- VIP17/MAL localized apically in both 2D and 3D cultures.
- VIP17/MAL overexpression led to increased formation of multilumen cysts.
- Aberrant apical marker (gp135) sorting to primary cilia and shortened or absent cilia were observed in VIP17/MAL overexpressing cells and transgenic mouse kidneys.
Conclusions:
- VIP17/MAL overexpression disrupts epithelial cell organization and primary cilium formation.
- Abnormalities in cilia structure and function are associated with VIP17/MAL-induced renal cyst development.
- VIP17/MAL-induced cystogenesis in mice likely occurs secondary to primary ciliary defects.
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