@article { , title = {Investigation of the transforming growth factor-beta 1 signalling pathway as a possible link between hyperphosphataemia and renal fibrosis in feline chronic kidney disease}, abstract = {Chronic kidney disease (CKD) is common in geriatric cats, and is characterised in the majority of cases by tubulointerstitial inflammation and fibrosis. Hyperphosphataemia is a frequent complication of CKD and is independently associated with severity of renal fibrosis and disease progression. Transforming growth factor-beta 1 (TGF-β1) signalling is thought to be a convergent pathway which mediates the progression of renal fibrosis in CKD. The aims of this study were to explore the interaction between increased extracellular phosphate and the TGF-β1 signalling pathway by investigating: (a) the effect of a commercially available, phosphate-restricted, diet on urinary TGF-β1 excretion in cats with CKD; and (b) the role of increased extracellular phosphate in regulating proliferation, apoptosis, and expression of genes related to TGF-β1 signalling and extracellular matrix (ECM) production in feline proximal tubular epithelial cells (FPTEC) and cortical fibroblasts from cats with azotaemic CKD (CKD-FCF). The dietary intervention study revealed no effect of dietary phosphate restriction on urinary active TGF-β1 excretion after 4–8 weeks (P = 0.98), despite significantly decreasing serum phosphate (P < 0.001). There was no effect of increased growth media phosphate concentration (from 0.95 mM to 2 mM and 3.5 mM) on proliferation (P = 0.99) and apoptotic activity in FPTEC (P = 0.22), or expression of genes related to ECM production and the TGF-β1 signalling pathway in FPTEC and CKD-FCF (P > 0.05). These findings suggest the beneficial effects of dietary phosphate restriction on progression of feline CKD may not occur through modulation of renal TGF-β1 production, and do not support a direct pro-fibrotic effect of increased extracellular phosphate on feline renal cells.}, doi = {10.1016/j.tvjl.2020.105582}, issn = {1090-0233}, journal = {The Veterinary Journal}, pages = {105582}, publicationstatus = {Published}, publisher = {Elsevier}, url = {https://rvc-repository.worktribe.com/output/1549418}, volume = {267}, keyword = {Animal Science and Zoology, General Veterinary}, year = {2020}, author = {Lawson, J.S. and Syme, H.M. and Wheeler-Jones, C.P.D. and Elliott, J.} }