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Differential regulation of angiotensin converting enzyme 2 and nuclear factor-κB by angiotensin II receptor subtypes in type 2 diabetic kidney.
Biochimie. 2015 Nov; 118:71-81.B

Abstract

Angiotensin II (Ang II) acts through Angiotensin Converting Enzyme (ACE)/Ang II type 1 receptor (AT1R) axis to promote renal failure whereas the Ang II type 2 receptor (AT2R)/Angiotensin Converting Enzyme 2 (ACE2)/Ang1-7/Mas axis constitutes the protective arm of Renin Angiotensin System (RAS). Though Ang II has been known to activate the Nuclear Factor-κB (NF-κB) signalling pathway through different receptor subtype(s) in different tissues under various diseases, the subtype orchestrating this stimulation in type 2 diabetic kidney remains elusive. ACE2, a protective monocarboxypeptidase, responsible for conversion of Ang II to Ang1-7, opposes the deleterious effects of RAS pathway but how its expression is altered with blockade of AT1R and AT2R is not yet known. Hence, the present study was conceived to understand the regulation of NF-κB and ACE2 by using specific AT1 and AT2 receptor antagonists in non-genetic model of type 2 diabetic nephropathy. Our results show that the AT1R and AT2R antagonists lead to the repression and activation of NF-κB signalling pathway, respectively which suggests the role of AT1R in NF-κB activation. The blockade of AT2R led to an increase in ACE2 expression, which may be a compensatory response to the drastically increased inflammatory mediators and oxidative stress in the diabetic kidney. To the best of our knowledge, this is the first study showing the differential regulation of NF-κB and ACE2 by Ang II receptor subtypes and thus this study improves our understanding regarding regulation of inflammatory cascade and ACE2 by AT1R and AT2R in type 2 diabetic kidney, which may help in designing novel strategies to combat the disease in future.

Authors+Show Affiliations

Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan, 333031, India.Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan, 333031, India.Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan, 333031, India.Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan, 333031, India.Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan, 333031, India. Electronic address: anil.gaikwad@pilani.bits-pilani.ac.in.

Pub Type(s)

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

Language

eng

PubMed ID

26271886

Citation

Pandey, Anuradha, et al. "Differential Regulation of Angiotensin Converting Enzyme 2 and Nuclear factor-κB By Angiotensin II Receptor Subtypes in Type 2 Diabetic Kidney." Biochimie, vol. 118, 2015, pp. 71-81.
Pandey A, Goru SK, Kadakol A, et al. Differential regulation of angiotensin converting enzyme 2 and nuclear factor-κB by angiotensin II receptor subtypes in type 2 diabetic kidney. Biochimie. 2015;118:71-81.
Pandey, A., Goru, S. K., Kadakol, A., Malek, V., & Gaikwad, A. B. (2015). Differential regulation of angiotensin converting enzyme 2 and nuclear factor-κB by angiotensin II receptor subtypes in type 2 diabetic kidney. Biochimie, 118, 71-81. https://doi.org/10.1016/j.biochi.2015.08.005
Pandey A, et al. Differential Regulation of Angiotensin Converting Enzyme 2 and Nuclear factor-κB By Angiotensin II Receptor Subtypes in Type 2 Diabetic Kidney. Biochimie. 2015;118:71-81. PubMed PMID: 26271886.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential regulation of angiotensin converting enzyme 2 and nuclear factor-κB by angiotensin II receptor subtypes in type 2 diabetic kidney. AU - Pandey,Anuradha, AU - Goru,Santosh Kumar, AU - Kadakol,Almesh, AU - Malek,Vajir, AU - Gaikwad,Anil Bhanudas, Y1 - 2015/08/10/ PY - 2015/03/04/received PY - 2015/08/05/accepted PY - 2015/8/15/entrez PY - 2015/8/15/pubmed PY - 2016/8/25/medline KW - ACE2 KW - AT1 receptor KW - AT2 receptor KW - NF-кB signalling pathway KW - Oxidative stress SP - 71 EP - 81 JF - Biochimie JO - Biochimie VL - 118 N2 - Angiotensin II (Ang II) acts through Angiotensin Converting Enzyme (ACE)/Ang II type 1 receptor (AT1R) axis to promote renal failure whereas the Ang II type 2 receptor (AT2R)/Angiotensin Converting Enzyme 2 (ACE2)/Ang1-7/Mas axis constitutes the protective arm of Renin Angiotensin System (RAS). Though Ang II has been known to activate the Nuclear Factor-κB (NF-κB) signalling pathway through different receptor subtype(s) in different tissues under various diseases, the subtype orchestrating this stimulation in type 2 diabetic kidney remains elusive. ACE2, a protective monocarboxypeptidase, responsible for conversion of Ang II to Ang1-7, opposes the deleterious effects of RAS pathway but how its expression is altered with blockade of AT1R and AT2R is not yet known. Hence, the present study was conceived to understand the regulation of NF-κB and ACE2 by using specific AT1 and AT2 receptor antagonists in non-genetic model of type 2 diabetic nephropathy. Our results show that the AT1R and AT2R antagonists lead to the repression and activation of NF-κB signalling pathway, respectively which suggests the role of AT1R in NF-κB activation. The blockade of AT2R led to an increase in ACE2 expression, which may be a compensatory response to the drastically increased inflammatory mediators and oxidative stress in the diabetic kidney. To the best of our knowledge, this is the first study showing the differential regulation of NF-κB and ACE2 by Ang II receptor subtypes and thus this study improves our understanding regarding regulation of inflammatory cascade and ACE2 by AT1R and AT2R in type 2 diabetic kidney, which may help in designing novel strategies to combat the disease in future. SN - 1638-6183 UR - https://www.unboundmedicine.com/medline/citation/26271886/Differential_regulation_of_angiotensin_converting_enzyme_2_and_nuclear_factor_κB_by_angiotensin_II_receptor_subtypes_in_type_2_diabetic_kidney_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0300-9084(15)00252-7 DB - PRIME DP - Unbound Medicine ER -