Renoprotective effect of a dipeptidyl peptidase-4 inhibitor on aging mice

Tae H. Ban; Eun N. Kim; Min Y. Kim; Ji H. Lim; Jong H. Lee; Hyung D. Kim; Hye E. Yoon; Cheol W. Park; Bum S. Choi

doi:10.14336/AD.2019.0620

Renoprotective effect of a dipeptidyl peptidase-4 inhibitor on aging mice

Tae H. Ban, Eun N. Kim, Min Y. Kim, Ji H. Lim, Jong H. Lee, Hyung D. Kim, Hye E. Yoon, Cheol W. Park, Bum S. Choi

Department of Internal Medicine

The Catholic University of Korea

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

Dipeptidyl peptidase 4 (DPP-4) inhibitors exert pleiotropic effects beyond glycemic control. We investigated the renoprotective effects of DPP-4 inhibitors on aging mice mediated by the renin-angiotensin system (RAS). C57BL/6 mice were divided into three groups: the two-month-old mice (YM group), the eighteen-month-old mice (AM group) and the eighteen-month-old, linagliptin-treated mice (AM + LIN group). Renal function was improved, based on serum creatinine and cystatin-C levels (p < 0.05 compared with the AM group for both parameters). Fibrotic areas and the levels of proteins related to fibrosis improved in the AM + LIN group (p < 0.001 compared with the AM group for all parameters). In the AM + LIN group, the DPP-4-positive area and activity and expressions of DPP-4 were decreased (p < 0.05 compared with the AM group for all parameters). The levels of proteins related to the RAS, including prorenin receptor, angiotensin-converting enzyme, angiotensin II and angiotensin 1 receptor, were decreased in the AM + LIN group (p < 0.05, p < 0.01, p < 0.05, and p < 0.01 compared with the AM group, respectively). NADPH oxidase 2 and NADPH oxidase 4 levels decreased in the AM + LIN group (p < 0.001 compared with the AM group for both proteins), whereas the levels of endothelial nitric oxide synthase (eNOS) phosphorylated at serine¹¹⁷⁷ and superoxide dismutase 1 were increased (p < 0.01 compared with the AM group for both proteins). DPP-4 inhibitors may exert renoprotective effects via prorenin receptor/angiotensin-converting enzyme/angiotensin II/angiotensin 1 receptor axis.

Original language	English
Pages (from-to)	588-602
Number of pages	15
Journal	Aging and Disease
Volume	11
Issue number	3
DOIs	https://doi.org/10.14336/AD.2019.0620
State	Published - 1 May 2020

Bibliographical note

Publisher Copyright:
Copyright: © 2019 Ban TH et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Keywords

Aging
Aging kidney
Dipeptidyl peptidase 4
Renin-angiotensin system
Renoprotective effect

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10.14336/AD.2019.0620

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title = "Renoprotective effect of a dipeptidyl peptidase-4 inhibitor on aging mice",

abstract = "Dipeptidyl peptidase 4 (DPP-4) inhibitors exert pleiotropic effects beyond glycemic control. We investigated the renoprotective effects of DPP-4 inhibitors on aging mice mediated by the renin-angiotensin system (RAS). C57BL/6 mice were divided into three groups: the two-month-old mice (YM group), the eighteen-month-old mice (AM group) and the eighteen-month-old, linagliptin-treated mice (AM + LIN group). Renal function was improved, based on serum creatinine and cystatin-C levels (p < 0.05 compared with the AM group for both parameters). Fibrotic areas and the levels of proteins related to fibrosis improved in the AM + LIN group (p < 0.001 compared with the AM group for all parameters). In the AM + LIN group, the DPP-4-positive area and activity and expressions of DPP-4 were decreased (p < 0.05 compared with the AM group for all parameters). The levels of proteins related to the RAS, including prorenin receptor, angiotensin-converting enzyme, angiotensin II and angiotensin 1 receptor, were decreased in the AM + LIN group (p < 0.05, p < 0.01, p < 0.05, and p < 0.01 compared with the AM group, respectively). NADPH oxidase 2 and NADPH oxidase 4 levels decreased in the AM + LIN group (p < 0.001 compared with the AM group for both proteins), whereas the levels of endothelial nitric oxide synthase (eNOS) phosphorylated at serine1177 and superoxide dismutase 1 were increased (p < 0.01 compared with the AM group for both proteins). DPP-4 inhibitors may exert renoprotective effects via prorenin receptor/angiotensin-converting enzyme/angiotensin II/angiotensin 1 receptor axis.",

keywords = "Aging, Aging kidney, Dipeptidyl peptidase 4, Renin-angiotensin system, Renoprotective effect",

author = "Ban, {Tae H.} and Kim, {Eun N.} and Kim, {Min Y.} and Lim, {Ji H.} and Lee, {Jong H.} and Kim, {Hyung D.} and Yoon, {Hye E.} and Park, {Cheol W.} and Choi, {Bum S.}",

note = "Publisher Copyright: Copyright: {\textcopyright} 2019 Ban TH et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

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AU - Ban, Tae H.

AU - Kim, Eun N.

AU - Kim, Min Y.

AU - Lim, Ji H.

AU - Lee, Jong H.

AU - Kim, Hyung D.

AU - Yoon, Hye E.

AU - Park, Cheol W.

AU - Choi, Bum S.

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PY - 2020/5/1

Y1 - 2020/5/1

N2 - Dipeptidyl peptidase 4 (DPP-4) inhibitors exert pleiotropic effects beyond glycemic control. We investigated the renoprotective effects of DPP-4 inhibitors on aging mice mediated by the renin-angiotensin system (RAS). C57BL/6 mice were divided into three groups: the two-month-old mice (YM group), the eighteen-month-old mice (AM group) and the eighteen-month-old, linagliptin-treated mice (AM + LIN group). Renal function was improved, based on serum creatinine and cystatin-C levels (p < 0.05 compared with the AM group for both parameters). Fibrotic areas and the levels of proteins related to fibrosis improved in the AM + LIN group (p < 0.001 compared with the AM group for all parameters). In the AM + LIN group, the DPP-4-positive area and activity and expressions of DPP-4 were decreased (p < 0.05 compared with the AM group for all parameters). The levels of proteins related to the RAS, including prorenin receptor, angiotensin-converting enzyme, angiotensin II and angiotensin 1 receptor, were decreased in the AM + LIN group (p < 0.05, p < 0.01, p < 0.05, and p < 0.01 compared with the AM group, respectively). NADPH oxidase 2 and NADPH oxidase 4 levels decreased in the AM + LIN group (p < 0.001 compared with the AM group for both proteins), whereas the levels of endothelial nitric oxide synthase (eNOS) phosphorylated at serine1177 and superoxide dismutase 1 were increased (p < 0.01 compared with the AM group for both proteins). DPP-4 inhibitors may exert renoprotective effects via prorenin receptor/angiotensin-converting enzyme/angiotensin II/angiotensin 1 receptor axis.

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KW - Aging kidney

KW - Dipeptidyl peptidase 4

KW - Renin-angiotensin system

KW - Renoprotective effect

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DO - 10.14336/AD.2019.0620

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JO - Aging and Disease

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ER -

Renoprotective effect of a dipeptidyl peptidase-4 inhibitor on aging mice

Abstract

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Keywords

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