ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on Twitter

Kidney Week

Abstract: PO1711

Signaling at the Mesangial Cell (MC) Membrane in Light Chain Deposition Disease (LCDD) and AL-Amyloidosis (AL-Am) Involves Sortilin-Related Receptor (SORL1), Caveolins, and C-Fos

Session Information

Category: Glomerular Diseases

  • 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix


  • Teng, Jiamin, University of South Alabama, Mobile, Alabama, United States
  • Zeng, Chun, University of South Alabama, Mobile, Alabama, United States
  • Turbat-Herrera, Elba A., University of South Alabama, Mobile, Alabama, United States
  • Moriyama, Takahito, Tokyo Joshi Ika Daigaku Fuzoku Kogenbyo Ryumachi Tsufu Center, Shinjuku-ku, Tokyo, Japan
  • Del Pozo-Yauner, Luis, University of South Alabama, Mobile, Alabama, United States
  • Liu, Bing, University of South Alabama, Mobile, Alabama, United States
  • Shen, Xinggui, Louisiana State University Health Sciences Center Shreveport, Shreveport, Louisiana, United States
  • Herrera, Guillermo A., University of South Alabama, Mobile, Alabama, United States

Group or Team Name

  • Department of Pathology, University of South Alabama

AL-Am and LCDD are two diametrically opposed glomerulopathies in terms of mesangial alterations produced by glomerulopathic light chains (GLCs). Their pathogenesis involves surface MC interactions resulting in cytoskeletal changes, c-fos translocation, phenotypic transformations, lysosomal activation (AL-Am), rough endoplasmic reticulum expansion (LCDD), and ultimately, mesangial matrix alterations. The present study addressed signaling pathways involved.


Human (H) MCs (both caveolin 1- wild type / knock-out) were incubated with monoclonal LCs purified from the urine of renal biopsy-proven AL-Am, LCDD, myeloma cast nephropathy (MCN) patients or albumin for up to 96 hours at different time frames. The samples were analyzed using light, immunofluorescence and electron microscopy, including immunolabeling for c-fos, kappa / lambda light LCs, caveolin-1 and SORL1.


Co-localizations in cup-shaped MC membrane indentations (caveolae) of GLCs with caveolin-1, and SORL1 were documented using double immunofluorescence and immunogold labeling ultrastructural techniques. Upon interactions with GLC (but not MCNLCs or albumin) caveolae on the surface of MCs increased dramatically, SORL1 was activated and c-fos translocated from cytoplasm to nuclei.


SORL1 is a key component of GLCs signal transduction in MCs. Co-localization supported the notion that Interactions of GLCs with MCs occurred in caveolae activating SORL1. Caveolin-1 knock out HMCs abolished c-fos translocation from cytoplasm to nuclei and the downstream mesangial alterations (i.e. mesangial expansion / increased protein production) in LCDD group. In ALLC group, c-fos translocation and amyloid production were decreased but not totally abolished, suggesting that other mechanism may be involved in amyloidogenesis. C-fos plays a crucial role following SORL1 activation to promote mesangial cell phenotypic transformation essential for amyloidogenesis and extracellular matrix over production, in AL-amyloidosis and LCDD, respectively.


  • Private Foundation Support