Interleukin-1 induces tubular epithelial-myofibroblast transdifferentiation through a transforming growth factor-beta1-dependent mechanism in vitro. Export

@article{citeulike:4116007, abstract = {Interleukin-1 (IL-1) has been shown to exert profibrotic activity in a number of disease models, including crescentic glomerulonephritis and pulmonary fibrosis, but the mechanisms by which this operates are poorly understood. Recent studies have identified a novel mechanism promoting renal fibrosis: tubular epithelial-myofibroblast transdifferentiation (TEMT). The present study examined whether IL-1 can stimulate TEMT in vitro. Cells of the normal rat kidney tubular epithelial cell line (NRK52E) were grown to confluence on collagen-coated plates and cultured for 5 days in the presence 1 to 20 ng/mL of IL-1alpha. Doses of 10 to 20 ng/mL of IL-1 caused transdifferentiation of NRK52E cells into myofibroblast-like cells. Scanning electron microscopy identified IL-1-induced morphological changes as a loss of apical-basal polarity and microvilli, cell hypertrophy, and the development of an elongated and invasive appearance. Phenotypically, IL-1-induced TEMT was characterized by de novo messenger RNA and protein expression of the mesenchymal marker alpha-smooth muscle actin, shown by Northern blotting, immunohistochemistry, and Western blotting. This was accompanied by loss of the epithelial marker E-cadherin. The addition of an excess of IL-1-receptor antagonist completely inhibited IL-1-induced TEMT. IL-1 was shown to stimulate the secretion of active transforming growth factor-beta1 (TGF-beta1) by NRK52E cells. Furthermore, the addition of a neutralizing anti-TGF-beta1 antibody inhibited IL-1-induced TEMT. In conclusion, IL-1 is a profibrogenic cytokine capable of inducing TEMT through a TGF-beta1-dependent mechanism. This may represent a novel mechanism by which IL-1 induces renal fibrosis in vivo.}, author = {Fan, J. M. and Huang, X. R. and Ng, Y. Y. and Nikolic-Paterson, D. J. and Mu, W. and Atkins, R. C. and Lan, H. Y.}, citeulike-article-id = {4116007}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/11273883}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=11273883}, issn = {1523-6838}, journal = {American journal of kidney diseases : the official journal of the National Kidney Foundation}, keywords = {emt, il1, nrk52e, pt, tgfb}, month = {April}, number = {4}, pages = {820--831}, posted-at = {2009-03-01 03:29:47}, priority = {2}, title = {Interleukin-1 induces tubular epithelial-myofibroblast transdifferentiation through a transforming growth factor-beta1-dependent mechanism in vitro.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/11273883}, volume = {37}, year = {2001} }

TY - JOUR ID - citeulike:4116007 L3 - citeulike-article-id:4116007 N2 - Interleukin-1 (IL-1) has been shown to exert profibrotic activity in a number of disease models, including crescentic glomerulonephritis and pulmonary fibrosis, but the mechanisms by which this operates are poorly understood. Recent studies have identified a novel mechanism promoting renal fibrosis: tubular epithelial-myofibroblast transdifferentiation (TEMT). The present study examined whether IL-1 can stimulate TEMT in vitro. Cells of the normal rat kidney tubular epithelial cell line (NRK52E) were grown to confluence on collagen-coated plates and cultured for 5 days in the presence 1 to 20 ng/mL of IL-1alpha. Doses of 10 to 20 ng/mL of IL-1 caused transdifferentiation of NRK52E cells into myofibroblast-like cells. Scanning electron microscopy identified IL-1-induced morphological changes as a loss of apical-basal polarity and microvilli, cell hypertrophy, and the development of an elongated and invasive appearance. Phenotypically, IL-1-induced TEMT was characterized by de novo messenger RNA and protein expression of the mesenchymal marker alpha-smooth muscle actin, shown by Northern blotting, immunohistochemistry, and Western blotting. This was accompanied by loss of the epithelial marker E-cadherin. The addition of an excess of IL-1-receptor antagonist completely inhibited IL-1-induced TEMT. IL-1 was shown to stimulate the secretion of active transforming growth factor-beta1 (TGF-beta1) by NRK52E cells. Furthermore, the addition of a neutralizing anti-TGF-beta1 antibody inhibited IL-1-induced TEMT. In conclusion, IL-1 is a profibrogenic cytokine capable of inducing TEMT through a TGF-beta1-dependent mechanism. This may represent a novel mechanism by which IL-1 induces renal fibrosis in vivo. IS - 4 JF - American journal of kidney diseases : the official journal of the National Kidney Foundation SN - 1523-6838 EP - 831 TI - Interleukin-1 induces tubular epithelial-myofibroblast transdifferentiation through a transforming growth factor-beta1-dependent mechanism in vitro. VL - 37 SP - 820 KW - emt KW - il1 KW - nrk52e KW - pt KW - tgfb AU - Fan, JM AU - Huang, XR AU - Ng, YY AU - Nikolic-Paterson, DJ AU - Mu, W AU - Atkins, RC AU - Lan, HY PY - 2001/04// UR - http://view.ncbi.nlm.nih.gov/pubmed/11273883 ER -