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.
AdvertisementTGF-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.
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