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Angiotensin II induces human TGF-beta 1 promoter activation: similarity to hyperglycaemia.
Diabetologia. 2002 Jun; 45(6):890-8.D

Abstract

AIMS/HYPOTHESIS

Activation of the renal renin-angiotensin system has been implicated in the pathogenesis of diabetic nephropathy. Because previous in vitro studies demonstrated the angiotensin II (ang II)-mediated up-regulation of the prosclerotic transforming growth factor beta 1 (TGF) we studied the molecular mechanism of ang II-induced TGF-beta 1 gene activation.

METHODS

Mesangial cells were stimulated with 100 nmol/l ang II with or without inhibitors of protein kinase C (PKC) and p38 MAPK and the TGF-beta 1 promoter activity was determined by promoter-reporter assays. The effect of ang II on the binding of nuclear proteins to the regulatory AP-1 site B, previously shown to mediate the high glucose-response of the TGF-beta 1 promoter, was studied by electrophoretic mobility shift assays.

RESULTS

Ang II enhanced the activity of the TGF-beta1 promoter fragment -453/+11 approximately 1.6-fold. Mutation of each of two AP-1 binding sites or inhibition of the PKC- and p38 MAPK-dependent pathways blocked the ang II-stimulated activity completely. Furthermore, ang II activated the binding of nuclear proteins to the AP-1 box B of the TGF-beta 1 promoter. These effects were similar to those previously observed with high glucose. Co-incubation with ang II and high glucose had no additive effect on TGF-beta 1 promoter activity, protein binding to the AP-1 box B or activation of p38 MAPK.

CONCLUSION/INTERPRETATION

The findings indicate that ang II and hyperglycaemia stimulate the TGF-beta 1 gene activation through the same PKC- and p38 MAPK-dependent pathways by the same regulatory elements of the TGF-beta 1 promoter. Our data could also be relevant for e.g. hypertension-induced glomerulosclerosis.

Authors+Show Affiliations

Department of Internal Medicine, Division of Endocrinology, Metabolism and Pathobiochemistry, University of Tübingen, Tübingen, Germany.No 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

12107734

Citation

Weigert, C, et al. "Angiotensin II Induces Human TGF-beta 1 Promoter Activation: Similarity to Hyperglycaemia." Diabetologia, vol. 45, no. 6, 2002, pp. 890-8.
Weigert C, Brodbeck K, Klopfer K, et al. Angiotensin II induces human TGF-beta 1 promoter activation: similarity to hyperglycaemia. Diabetologia. 2002;45(6):890-8.
Weigert, C., Brodbeck, K., Klopfer, K., Häring, H. U., & Schleicher, E. D. (2002). Angiotensin II induces human TGF-beta 1 promoter activation: similarity to hyperglycaemia. Diabetologia, 45(6), 890-8.
Weigert C, et al. Angiotensin II Induces Human TGF-beta 1 Promoter Activation: Similarity to Hyperglycaemia. Diabetologia. 2002;45(6):890-8. PubMed PMID: 12107734.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Angiotensin II induces human TGF-beta 1 promoter activation: similarity to hyperglycaemia. AU - Weigert,C, AU - Brodbeck,K, AU - Klopfer,K, AU - Häring,H U, AU - Schleicher,E D, Y1 - 2002/05/17/ PY - 2001/11/12/received PY - 2002/02/19/revised PY - 2002/7/11/pubmed PY - 2003/1/22/medline PY - 2002/7/11/entrez SP - 890 EP - 8 JF - Diabetologia JO - Diabetologia VL - 45 IS - 6 N2 - AIMS/HYPOTHESIS: Activation of the renal renin-angiotensin system has been implicated in the pathogenesis of diabetic nephropathy. Because previous in vitro studies demonstrated the angiotensin II (ang II)-mediated up-regulation of the prosclerotic transforming growth factor beta 1 (TGF) we studied the molecular mechanism of ang II-induced TGF-beta 1 gene activation. METHODS: Mesangial cells were stimulated with 100 nmol/l ang II with or without inhibitors of protein kinase C (PKC) and p38 MAPK and the TGF-beta 1 promoter activity was determined by promoter-reporter assays. The effect of ang II on the binding of nuclear proteins to the regulatory AP-1 site B, previously shown to mediate the high glucose-response of the TGF-beta 1 promoter, was studied by electrophoretic mobility shift assays. RESULTS: Ang II enhanced the activity of the TGF-beta1 promoter fragment -453/+11 approximately 1.6-fold. Mutation of each of two AP-1 binding sites or inhibition of the PKC- and p38 MAPK-dependent pathways blocked the ang II-stimulated activity completely. Furthermore, ang II activated the binding of nuclear proteins to the AP-1 box B of the TGF-beta 1 promoter. These effects were similar to those previously observed with high glucose. Co-incubation with ang II and high glucose had no additive effect on TGF-beta 1 promoter activity, protein binding to the AP-1 box B or activation of p38 MAPK. CONCLUSION/INTERPRETATION: The findings indicate that ang II and hyperglycaemia stimulate the TGF-beta 1 gene activation through the same PKC- and p38 MAPK-dependent pathways by the same regulatory elements of the TGF-beta 1 promoter. Our data could also be relevant for e.g. hypertension-induced glomerulosclerosis. SN - 0012-186X UR - https://www.unboundmedicine.com/medline/citation/12107734/Angiotensin_II_induces_human_TGF_beta_1_promoter_activation:_similarity_to_hyperglycaemia_ L2 - https://doi.org/10.1007/s00125-002-0843-4 DB - PRIME DP - Unbound Medicine ER -