Betaglycan as a Potential Regulator of TGF-β1 Signalling in the Kidney

Mohamed Ali Al-helfawi, Aled Phiillips, Robert Steadman

Abstract


Before going deeper and deeper to study the kidney and its roles, let’s explain the main points that affects mechanisms through which it works. We start with transforming growth factor β1 (TGF-β1), which is a multifunctional growth factor with an important role in development, cell proliferation, matrix deposition, modulation of the, immunity, regulation of embryonic development and cellular differentiation and apoptosis (programmed cell death). It is considered as a significant mediator of glomerular and tubulointerstitial pathobiology in chronic kidney diseases[1]. Over-expression of TGF-β can induce renal fibrosis, causing kidney disease, and ultimately end-stage renal disease (ESRD). Recent developments have found that, using certain types of protein antagonists such as a  receptor ligand or drug that does not induce a biological response itself upon binding to a receptor but  sequential activation of two serine/threonine kinase receptors, the type I and type II receptors.  A third receptor, betaglycan serves as a co-receptor for TGF-β1. Recent reports indicate that membrane anchored betaglycan may play an inhibitory role in TGF-β1 signalling. This inhibitory role of betaglycan is a function of the heparan sulphate composition of the betaglycan glycosaminoglycan [2]. We can say that, the expression of betaglycan and its augmentation by cytokines treatment in HK2 cells has been described. By concentrating on TGF-β activity, it is shown that knock-down by siRNA and inhibition of glycoslation of  betaglycan antagonize signalling by TGF-β end production of EMT.  This work suggests that betaglycan could be a major mediator of PTC activation in vivo. blocks  reverse the effects of renal fibrosis [3].


Keywords


α-SMA;(Alpha- Smooth Muscle Actin). DNA; (Deoxyribonucleic Acid). ECM; (Extracellular Matrix). EMT; (Epithelial-Mesenchymal Transition). GAPDH; (Glyceraldehyde-3-phosphate dehydrogenase). HK-2 (Human Kidney-2). mRNA; (Messenger Ribonucleic Acid). PAGE; (P

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References


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