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Interaction between TGF-β and ACE2-Ang-(1-7)-Mas pathway in high glucose-cultured NRK-52E cells.
Mol Cell Endocrinol. 2013 Feb 05; 366(1):21-30.MC

Abstract

Transforming growth factor-β (TGF-β) is pivotal in diabetic nephropathy (DN). Angiotensin converting enzyme-2 (ACE2) converts angiotensin II (Ang II) to angiotensin 1-7 (Ang-(1-7)), which binds to Mas. Proximal tubular ACE2 is decreased in DN. ACE2 deficiency exacerbates whereas ACE2 overexpression attenuates DN. Thus, we investigated the mechanism of high glucose-decreased ACE2 in terms of the interaction between TGF-β and ACE2-Ang-(1-7)-Mas in NRK-52E cells. We found that high glucose increased TGF-β1. SB431542 attenuated high glucose-inhibited ACE2 and Mas and Ang-(1-7) conversion from Ang II while attenuating high glucose-induced fibronectin. TGF-β1 also decreased ACE2 and Mas and Ang-(1-7) conversion from Ang II. A779 attenuated Ang-(1-7)-decreased TGF-β1 and Ang-(1-7)-activated JAK2-STAT3. Moreover, A779, LY294002 and AG490 attenuated Ang-(1-7)-inhibited TGF-β1. The combination of Ang-(1-7) and Mas attenuated TGF-β1 (but not high glucose)-induced fibronectin. Thus, high glucose decreases ACE2 via TGF-βR in NRK-52E cells. Additionally, there is a negative feedback function between TGF-β and ACE2, and the combined inhibition of TGF-β and activation of the ACE2-Ang-(1-7)-Mas may be useful for treating diabetic renal fibrosis.

Authors+Show Affiliations

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan, ROC.No 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

23174757

Citation

Chou, Chi-Hsien, et al. "Interaction Between TGF-β and ACE2-Ang-(1-7)-Mas Pathway in High Glucose-cultured NRK-52E Cells." Molecular and Cellular Endocrinology, vol. 366, no. 1, 2013, pp. 21-30.
Chou CH, Chuang LY, Lu CY, et al. Interaction between TGF-β and ACE2-Ang-(1-7)-Mas pathway in high glucose-cultured NRK-52E cells. Mol Cell Endocrinol. 2013;366(1):21-30.
Chou, C. H., Chuang, L. Y., Lu, C. Y., & Guh, J. Y. (2013). Interaction between TGF-β and ACE2-Ang-(1-7)-Mas pathway in high glucose-cultured NRK-52E cells. Molecular and Cellular Endocrinology, 366(1), 21-30. https://doi.org/10.1016/j.mce.2012.11.004
Chou CH, et al. Interaction Between TGF-β and ACE2-Ang-(1-7)-Mas Pathway in High Glucose-cultured NRK-52E Cells. Mol Cell Endocrinol. 2013 Feb 5;366(1):21-30. PubMed PMID: 23174757.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interaction between TGF-β and ACE2-Ang-(1-7)-Mas pathway in high glucose-cultured NRK-52E cells. AU - Chou,Chi-Hsien, AU - Chuang,Lea-Yea, AU - Lu,Chi-Yu, AU - Guh,Jinn-Yuh, Y1 - 2012/11/19/ PY - 2012/05/10/received PY - 2012/10/04/revised PY - 2012/11/07/accepted PY - 2012/11/24/entrez PY - 2012/11/24/pubmed PY - 2013/8/8/medline SP - 21 EP - 30 JF - Molecular and cellular endocrinology JO - Mol Cell Endocrinol VL - 366 IS - 1 N2 - Transforming growth factor-β (TGF-β) is pivotal in diabetic nephropathy (DN). Angiotensin converting enzyme-2 (ACE2) converts angiotensin II (Ang II) to angiotensin 1-7 (Ang-(1-7)), which binds to Mas. Proximal tubular ACE2 is decreased in DN. ACE2 deficiency exacerbates whereas ACE2 overexpression attenuates DN. Thus, we investigated the mechanism of high glucose-decreased ACE2 in terms of the interaction between TGF-β and ACE2-Ang-(1-7)-Mas in NRK-52E cells. We found that high glucose increased TGF-β1. SB431542 attenuated high glucose-inhibited ACE2 and Mas and Ang-(1-7) conversion from Ang II while attenuating high glucose-induced fibronectin. TGF-β1 also decreased ACE2 and Mas and Ang-(1-7) conversion from Ang II. A779 attenuated Ang-(1-7)-decreased TGF-β1 and Ang-(1-7)-activated JAK2-STAT3. Moreover, A779, LY294002 and AG490 attenuated Ang-(1-7)-inhibited TGF-β1. The combination of Ang-(1-7) and Mas attenuated TGF-β1 (but not high glucose)-induced fibronectin. Thus, high glucose decreases ACE2 via TGF-βR in NRK-52E cells. Additionally, there is a negative feedback function between TGF-β and ACE2, and the combined inhibition of TGF-β and activation of the ACE2-Ang-(1-7)-Mas may be useful for treating diabetic renal fibrosis. SN - 1872-8057 UR - https://www.unboundmedicine.com/medline/citation/23174757/Interaction_between_TGF_β_and_ACE2_Ang__1_7__Mas_pathway_in_high_glucose_cultured_NRK_52E_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0303-7207(12)00496-0 DB - PRIME DP - Unbound Medicine ER -