Human TTRV30M localization within podocytes in a transgenic mouse model of transthyretin related amyloidosis: does the environment play a role?
Transthyretin related amyloidosis is a nosological entity that leads to disability, diminished quality of life, all stages of chronic kidney disease and eventually death. Podocytes are polarized, highly differentiated epithelial cells important for proper nephron function. In the present study we investigated whether deposited TTRVal30Met (TTRV30M) molecules could be localized within podocytes in situ under the effect of different housing conditions (i.e. specific pathogen free [SPF] vs. non-SPF). Murine renal glomeruli from human TTRV30M (hTTRV30M) transgenic mice were examined via direct and indirect immunofluorescence techniques for the presence of hTTRV30M, murine serum amyloid P, activated caspase-3 and NPHS1. Association strength and amount of colocalization for NPHS1-hTTRV30M, NPHS1-activated caspase-3, hTTRV30M-murine serum amyloid P were estimated. Localization of hTTRV30M in podocytes was demonstrated by immuno-electron microscopy. Renal hTTRV30M gene and NPHS1 gene expression levels were estimated. Non-SPF transgenic mice showed increased glomerular hTTRV30M deposition compared to their SPF counterparts. Furthermore increased podocytic localization of hTTRV30M was noticed in non-SPF mice. Glomerular caspase-3 activation was increased only in the non SPF housing conditions. Podocytic caspase-3 activation was increased in SPF and in non-SPF transgenic mice when compared to non transgenic controls. Environmental conditions influence glomerular deposition and podocytic localization of hTTRV30M. In this context increased caspase-3 activation occurred.
Department of Nephrology, Heraklion University Hospital, University of Crete, PO Box 1352, 71110, Heraklion, Crete, Greece. petrakgia@gmail.com
Ioannis
I
Petrakis
Vasiliki
V
Mavroeidi
Kostas
K
Stylianou
George
G
Efthymiou
Kostas
K
Perakis
Eleftheria
E
Vardaki
Spyridon
S
Stratigis
Kostas
K
Giannakakis
Kostas
K
Kourouniotis
George
G
Amoiridis
Andreas
A
Plaitakis
Maria Joao
MJ
Saraiva
Ken Ichi
KI
Yamamura
Eugene
E
Daphnis
D028227:Amyloid Neuropathies, Familial / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D059647:Gene-Environment Interaction; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016253:Microscopy, Immunoelectron; D050199:Podocytes / Q000378:metabolism / Q000648:ultrastructure; D011228:Prealbumin / Q000235:genetics / Q000378:metabolism
D011228:Prealbumin; D053148:Caspase 3