AL(light chain)-amyloidogenesis by mesangial cells involves active participation of lysosomes: An ultrastructural

Guillermo A Herrera1,2, Jiamin Teng3, Chun Zeng3

  • 1University of South Alabama, USA.

Heliyon
|April 25, 2023
PubMed

Insights

Kidney mesangial cells form amyloid fibrils within endosomes and lysosomes. This study reveals the complete sequence of amyloid fibril formation inside these specialized kidney cells.

Area of Science:

  • Nephrology
  • Cell Biology
  • Biochemistry

Background:

  • Amyloid formation is a stepwise process observed in macrophages.
  • Mesangial cells in the kidney can transform into macrophages and participate in amyloidogenesis.
  • The precise mechanism of amyloid fibril formation within cells remains unclear.

Purpose of the Study:

  • To dissect the ultrastructural sequence of amyloid fibril formation within human mesangial cells.
  • To investigate the role of endosomes and lysosomes in AL-amyloidogenesis.
  • To elucidate the cellular events during amyloid fibril assembly.

Main Methods:

  • Ultrastructural examination of lysosomal gradient specimens from human mesangial cells.
  • Incubation of human mesangial cells with AL-light chains (AL-LCs).
  • Time-course analysis of amyloid fibril formation.

Main Results:

  • Amyloid fibril formation initiates in endosomes.
  • Fibrillogenesis is completed and most prominent within the lysosomal compartment.
  • Amyloid fibrils were observed within 10 minutes of incubation in human mesangial cells.

Conclusions:

  • This study provides the first experimental demonstration of amyloid fibril formation inside human mesangial cells.
  • The complete sequence of AL-amyloidogenesis within these cells has been elucidated.
  • Endosomes and lysosomes are critical compartments for amyloid fibril assembly in mesangial cells.

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