A new study has linked a genetic marker, and related protein pathways to
poor outcomes in kidney transplantation. A small variation in the code of a key gene in a kidney donor may be
more likely to cause fibrosis (scar tissue accumulation) that contributes to
kidney failure in the transplant recipient. Build up of scar tissue interferes
with proper renal function. If the protein pathways that trigger kidney
fibrosis are uncovered, researchers can develop drugs that will help prevent
this disease process in kidney transplant recipients and patients with chronic
kidney disease. With further studies these findings can be used to better
screen potential donors and improve the transplant outcomes.
According to the new study, the single nucleotide polymorphisms (SNP)
rs17319721 in the gene SHROOM3, when present in the kidney donor, correlates
with increased expression of the SHROOM3 genes, and a greater quantity of
SHROOM3 protein in the organ once transplanted. More SHROOM3 turns on more
transcription factor 7-like 2 (TCF7L2), which, is a member of the Wnt signaling
pathway, ultimately resulting in increased signaling by transforming growth
factor beta 1 (TGF-β1) and increased COL1A1 (Collagen, type I, alpha 1) expression.
TGF-β1 signals for the building of connective tissue (scar tissue), as a
normal part of healing, but may also drive fibrosis in the wrong context.
COL1A1 is the gene that codes for the major component in type I collagen, the
major protein component of connective tissues like bone cartilage and of scar
tissue that forms as wounds heal. Together, both these factors contribute to
excessive tissue fibrosis.
"Further work is needed before a clinical application of the study can
be introduced. However, our results are a crucial and optimistic step towards
improving treatment of chronic kidney disease", said Dr. Barbara Murphy, MD,
Chair, Department of Medicine, Murray M. Rosenberg Professor of Medicine
(Nephrology) and Dean for Clinical Integration and Population Health at the
Icahn School of Medicine at Mount Sinai.
The study has been published in the Journal of Clinical Investigation.