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Role of Kruppel-like factor 6 in transforming growth factor-beta1-induced epithelial-mesenchymal transition of proximal tubule cells.
Am J Physiol Renal Physiol. 2008 Nov; 295(5):F1388-96.AJ

Abstract

Krüppel-like factor 6 (KLF6) is a DNA-binding protein containing a triple zinc-fingered motif and plays a key role in the regulation of cell proliferation, differentiation, and development. More recently it has been implicated in hepatic fibrosis via its binding to the transforming growth factor (TGF)-beta control element. In the kidney, epithelial-mesenchymal transition (EMT) is a major contributor to the pathogenesis of renal fibrosis, with TGF-beta1 being a key mediator of EMT. The present study aimed to determine the role of KLF6 and TGF-beta1 in EMT in proximal tubule cells. To determine the relevance in clinical disease, KLF6 was measured in kidneys of streptozotocin-induced diabetic Ren-2 rats and in cells exposed to high (30 mM) glucose. TGF-beta1 was confirmed to induce EMT by morphological change, loss of E-cadherin, and gain in vimentin expression. KLF6 mRNA expression was concomitantly measured. To determine the role of KLF6 in EMT, the above markers of EMT were determined in KLF6-silenced (small interfering RNA) and KLF6-overexpressing proximal tubule cells. KLF6 overexpression significantly promoted a phenotype consistent with EMT. High glucose induced KLF6 in proximal tubule cells (P < 0.05). This increase in KLF6 in response to high glucose was TGF-beta1 mediated. In an in vivo model of diabetic nephropathy KLF6 increased at week 8 (P < 0.05). KLF6 plays a permissive role in TGF-beta1-induced EMT in proximal tubule cells. Its upregulation in in vivo models of diabetic nephropathy suggests it as a potential therapeutic target.

Authors+Show Affiliations

Kolling Institute, Department of Medicine, Royal North Shore Hospital, Sydney.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18753303

Citation

Holian, John, et al. "Role of Kruppel-like Factor 6 in Transforming Growth Factor-beta1-induced Epithelial-mesenchymal Transition of Proximal Tubule Cells." American Journal of Physiology. Renal Physiology, vol. 295, no. 5, 2008, pp. F1388-96.
Holian J, Qi W, Kelly DJ, et al. Role of Kruppel-like factor 6 in transforming growth factor-beta1-induced epithelial-mesenchymal transition of proximal tubule cells. Am J Physiol Renal Physiol. 2008;295(5):F1388-96.
Holian, J., Qi, W., Kelly, D. J., Zhang, Y., Mreich, E., Pollock, C. A., & Chen, X. M. (2008). Role of Kruppel-like factor 6 in transforming growth factor-beta1-induced epithelial-mesenchymal transition of proximal tubule cells. American Journal of Physiology. Renal Physiology, 295(5), F1388-96. https://doi.org/10.1152/ajprenal.00055.2008
Holian J, et al. Role of Kruppel-like Factor 6 in Transforming Growth Factor-beta1-induced Epithelial-mesenchymal Transition of Proximal Tubule Cells. Am J Physiol Renal Physiol. 2008;295(5):F1388-96. PubMed PMID: 18753303.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of Kruppel-like factor 6 in transforming growth factor-beta1-induced epithelial-mesenchymal transition of proximal tubule cells. AU - Holian,John, AU - Qi,Weier, AU - Kelly,Darren J, AU - Zhang,Yuan, AU - Mreich,Ellein, AU - Pollock,Carol A, AU - Chen,Xin-Ming, Y1 - 2008/08/27/ PY - 2008/8/30/pubmed PY - 2009/2/10/medline PY - 2008/8/30/entrez SP - F1388 EP - 96 JF - American journal of physiology. Renal physiology JO - Am. J. Physiol. Renal Physiol. VL - 295 IS - 5 N2 - Krüppel-like factor 6 (KLF6) is a DNA-binding protein containing a triple zinc-fingered motif and plays a key role in the regulation of cell proliferation, differentiation, and development. More recently it has been implicated in hepatic fibrosis via its binding to the transforming growth factor (TGF)-beta control element. In the kidney, epithelial-mesenchymal transition (EMT) is a major contributor to the pathogenesis of renal fibrosis, with TGF-beta1 being a key mediator of EMT. The present study aimed to determine the role of KLF6 and TGF-beta1 in EMT in proximal tubule cells. To determine the relevance in clinical disease, KLF6 was measured in kidneys of streptozotocin-induced diabetic Ren-2 rats and in cells exposed to high (30 mM) glucose. TGF-beta1 was confirmed to induce EMT by morphological change, loss of E-cadherin, and gain in vimentin expression. KLF6 mRNA expression was concomitantly measured. To determine the role of KLF6 in EMT, the above markers of EMT were determined in KLF6-silenced (small interfering RNA) and KLF6-overexpressing proximal tubule cells. KLF6 overexpression significantly promoted a phenotype consistent with EMT. High glucose induced KLF6 in proximal tubule cells (P < 0.05). This increase in KLF6 in response to high glucose was TGF-beta1 mediated. In an in vivo model of diabetic nephropathy KLF6 increased at week 8 (P < 0.05). KLF6 plays a permissive role in TGF-beta1-induced EMT in proximal tubule cells. Its upregulation in in vivo models of diabetic nephropathy suggests it as a potential therapeutic target. SN - 1931-857X UR - https://www.unboundmedicine.com/medline/citation/18753303/Role_of_Kruppel_like_factor_6_in_transforming_growth_factor_beta1_induced_epithelial_mesenchymal_transition_of_proximal_tubule_cells_ L2 - http://www.physiology.org/doi/full/10.1152/ajprenal.00055.2008?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -