'Although we knew that faulty TRPC6 causes kidney disease, we did not know this protein had this anchoring role in the podocyte
until now,' explains Dr Farmer.
This causes podocyte
loss and breach of the filtration barrier, which leads to proteinuria, the hallmark of progressive kidney diseases such as FSGS, TR-MCD and DN.
Ultrastructural examination of the Malpighian corpuscles of the renal control and ginger extract treated rats revealed that Bowman's capsule visceral layer comprises of podocytes
. Each podocyte
has a cell body from which extended several primary foot processes.
The study, published in Nature Communications, saw a global research team, led by the University of Bristol study how the activity of the enzyme GSK3 (Glycogen Synthase Kinase 3) affects the function of podocyte
cells, which are crucial in enabling the kidneys to filter blood.
More notably, a previous study reported that GSK3[beta] was a target of miR-135 family including miR-135a and miR-135b, which both played an important role in the development of podocyte
injury and the disorder of the podocyte
injury relevant in diabetic nephropathy?
As recently hypothesized, in patients with celiac disease, the increased intestinal permeability or "leaky gut" acts as a driving force in bacterial translocation and subsequent circulation of lipopolysaccharides which in turn cause podocyte
damage in the kidneys [10, 11].
(a and b) BSA group shows subepithelial electron-dense deposits, GBM loss of trilaminar structure, podocyte
swelling, and loss of foot processes.
(2-4) Glomerular podocyte
injury causes proteinuria and results in tubular and interstitial injury.
Glucocorticoids have direct effect on podocyte
by increasing the number of myeloid suppressor cells which downregulate T cell function13,14 and their use in patients with solitary kidney with persistent proteinuria despite being on supportive therapy have not been under taken so far to definitely establish their role and efficacy in preventing renal failure, but prior studies on the combination of an immunosuppressive agent (mycophenolate mofetil) to the ACE inhibitor (or an angiotensin II receptor antagonist) in decreasing hematopoietic cell infiltration and proteinuria have been documented15,16.
Previous evidence shows that a possible mechanism of proteinuria is complex, and may be linked to glomerular podocyte
protection, inflammation associated with podocyte
damage, cell adhesion, and space conformation of cytoskeletal proteins [2,13].
There are many valuable uses for this protocol of mature podocyte
generation, including investigating the steps involved in the differentiation of podocytes
from their progenitor cells (a process which remains largely unknown); studying the source and progression of various kidney diseases including podocyto-pathies and glomerulosclerosis; and establishing in vitro systems for kidney drug testing and discovery, such as the Glomerulus Chip.