Angiotensin II type 2 receptor correlates with therapeutic effects of losartan in rats with adjuvant-induced arthritis

Di Wang, Shanshan Hu, Jie Zhu, Jun Yuan, Jingjing Wu, Aiwu Zhou, Yujing Wu, Wendi Zhao, Qiong Huang, Yan Chang, Qingtong Wang, Wuyi Sun, Wei Wei

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The angiotensin II type 1 receptor (AT1R) blocker losartan ameliorates rheumatoid arthritis (RA) in an experimental model. In RA, AT2R mainly opposes AT1R, but the mechanism by which this occurs still remains obscure. In the present study, we investigated the role of AT2R in the treatment of rats with adjuvant-induced arthritis (AIA) by losartan. Adjuvant-induced arthritis rats were treated with losartan (5, 10 and 15 mg/kg) and methotrexate (MTX; 0.5 mg/kg) in vivo from day 14 to day 28. Arthritis was evaluated by the arthritis index and histological examination. Angiotensin II, tumour necrosis factor-α, and VEGF levels were examined by ELISA. The expression of AT1R and AT2R was detected by western blot and immunohistochemistry analysis. After stimulation with interleukin-1β in vitro, the effects of the AT2R agonist CGP42112 (10-8-10-5 M) on the chemotaxis of monocytes induced by 10% foetal calf serum (FCS) were analysed by using Transwell assay. Subsequently, the therapeutic effects of CGP42112 (5, 10 and 20 μg/kg) were evaluated in vivo by intra-articular injection in AIA rats. After treatment with losartan, the down-regulation of AT1R expression and up-regulation of AT2R expression in the spleen and synovium of AIA rats correlated positively with reduction in the polyarthritis index. Treatment with CGP42112 inhibited the chemotaxis of AIA monocytes in vitro, possibly because of the up-regulation of AT2R expression. Intra-articular injection with CGP42112 (10 and 20 μg/kg) ameliorated the arthritis index and histological signs of arthritis. In summary, the present study strongly suggests that the up-regulation of AT2R might be an additional mechanism by which losartan exerts its therapeutic effects in AIA rats.

Original languageEnglish (US)
Pages (from-to)1577-1587
Number of pages11
JournalJournal of Cellular and Molecular Medicine
Volume17
Issue number12
DOIs
StatePublished - Dec 1 2013
Externally publishedYes

Fingerprint

Angiotensin Type 2 Receptor
Experimental Arthritis
Losartan
Therapeutic Uses
Arthritis
Angiotensin Type 1 Receptor
Intra-Articular Injections
Up-Regulation
Chemotaxis
Monocytes
Rheumatoid Arthritis
Angiotensin II Type 1 Receptor Blockers
Synovial Membrane
Interleukin-1
Methotrexate
Angiotensin II
Vascular Endothelial Growth Factor A
Theoretical Models
Therapeutics
Down-Regulation

Keywords

  • Adjuvant-induced arthritis
  • Angiotensin II type 2 receptor
  • Losartan
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

Cite this

Angiotensin II type 2 receptor correlates with therapeutic effects of losartan in rats with adjuvant-induced arthritis. / Wang, Di; Hu, Shanshan; Zhu, Jie; Yuan, Jun; Wu, Jingjing; Zhou, Aiwu; Wu, Yujing; Zhao, Wendi; Huang, Qiong; Chang, Yan; Wang, Qingtong; Sun, Wuyi; Wei, Wei.

In: Journal of Cellular and Molecular Medicine, Vol. 17, No. 12, 01.12.2013, p. 1577-1587.

Research output: Contribution to journalArticle

Wang, D, Hu, S, Zhu, J, Yuan, J, Wu, J, Zhou, A, Wu, Y, Zhao, W, Huang, Q, Chang, Y, Wang, Q, Sun, W & Wei, W 2013, 'Angiotensin II type 2 receptor correlates with therapeutic effects of losartan in rats with adjuvant-induced arthritis', Journal of Cellular and Molecular Medicine, vol. 17, no. 12, pp. 1577-1587. https://doi.org/10.1111/jcmm.12128
Wang, Di ; Hu, Shanshan ; Zhu, Jie ; Yuan, Jun ; Wu, Jingjing ; Zhou, Aiwu ; Wu, Yujing ; Zhao, Wendi ; Huang, Qiong ; Chang, Yan ; Wang, Qingtong ; Sun, Wuyi ; Wei, Wei. / Angiotensin II type 2 receptor correlates with therapeutic effects of losartan in rats with adjuvant-induced arthritis. In: Journal of Cellular and Molecular Medicine. 2013 ; Vol. 17, No. 12. pp. 1577-1587.
@article{472b40484b32491aa37ccb9acf08efb9,
title = "Angiotensin II type 2 receptor correlates with therapeutic effects of losartan in rats with adjuvant-induced arthritis",
abstract = "The angiotensin II type 1 receptor (AT1R) blocker losartan ameliorates rheumatoid arthritis (RA) in an experimental model. In RA, AT2R mainly opposes AT1R, but the mechanism by which this occurs still remains obscure. In the present study, we investigated the role of AT2R in the treatment of rats with adjuvant-induced arthritis (AIA) by losartan. Adjuvant-induced arthritis rats were treated with losartan (5, 10 and 15 mg/kg) and methotrexate (MTX; 0.5 mg/kg) in vivo from day 14 to day 28. Arthritis was evaluated by the arthritis index and histological examination. Angiotensin II, tumour necrosis factor-α, and VEGF levels were examined by ELISA. The expression of AT1R and AT2R was detected by western blot and immunohistochemistry analysis. After stimulation with interleukin-1β in vitro, the effects of the AT2R agonist CGP42112 (10-8-10-5 M) on the chemotaxis of monocytes induced by 10{\%} foetal calf serum (FCS) were analysed by using Transwell assay. Subsequently, the therapeutic effects of CGP42112 (5, 10 and 20 μg/kg) were evaluated in vivo by intra-articular injection in AIA rats. After treatment with losartan, the down-regulation of AT1R expression and up-regulation of AT2R expression in the spleen and synovium of AIA rats correlated positively with reduction in the polyarthritis index. Treatment with CGP42112 inhibited the chemotaxis of AIA monocytes in vitro, possibly because of the up-regulation of AT2R expression. Intra-articular injection with CGP42112 (10 and 20 μg/kg) ameliorated the arthritis index and histological signs of arthritis. In summary, the present study strongly suggests that the up-regulation of AT2R might be an additional mechanism by which losartan exerts its therapeutic effects in AIA rats.",
keywords = "Adjuvant-induced arthritis, Angiotensin II type 2 receptor, Losartan, Rheumatoid arthritis",
author = "Di Wang and Shanshan Hu and Jie Zhu and Jun Yuan and Jingjing Wu and Aiwu Zhou and Yujing Wu and Wendi Zhao and Qiong Huang and Yan Chang and Qingtong Wang and Wuyi Sun and Wei Wei",
year = "2013",
month = "12",
day = "1",
doi = "10.1111/jcmm.12128",
language = "English (US)",
volume = "17",
pages = "1577--1587",
journal = "Journal of Cellular and Molecular Medicine",
issn = "1582-1838",
publisher = "Wiley-Blackwell",
number = "12",

}

TY - JOUR

T1 - Angiotensin II type 2 receptor correlates with therapeutic effects of losartan in rats with adjuvant-induced arthritis

AU - Wang, Di

AU - Hu, Shanshan

AU - Zhu, Jie

AU - Yuan, Jun

AU - Wu, Jingjing

AU - Zhou, Aiwu

AU - Wu, Yujing

AU - Zhao, Wendi

AU - Huang, Qiong

AU - Chang, Yan

AU - Wang, Qingtong

AU - Sun, Wuyi

AU - Wei, Wei

PY - 2013/12/1

Y1 - 2013/12/1

N2 - The angiotensin II type 1 receptor (AT1R) blocker losartan ameliorates rheumatoid arthritis (RA) in an experimental model. In RA, AT2R mainly opposes AT1R, but the mechanism by which this occurs still remains obscure. In the present study, we investigated the role of AT2R in the treatment of rats with adjuvant-induced arthritis (AIA) by losartan. Adjuvant-induced arthritis rats were treated with losartan (5, 10 and 15 mg/kg) and methotrexate (MTX; 0.5 mg/kg) in vivo from day 14 to day 28. Arthritis was evaluated by the arthritis index and histological examination. Angiotensin II, tumour necrosis factor-α, and VEGF levels were examined by ELISA. The expression of AT1R and AT2R was detected by western blot and immunohistochemistry analysis. After stimulation with interleukin-1β in vitro, the effects of the AT2R agonist CGP42112 (10-8-10-5 M) on the chemotaxis of monocytes induced by 10% foetal calf serum (FCS) were analysed by using Transwell assay. Subsequently, the therapeutic effects of CGP42112 (5, 10 and 20 μg/kg) were evaluated in vivo by intra-articular injection in AIA rats. After treatment with losartan, the down-regulation of AT1R expression and up-regulation of AT2R expression in the spleen and synovium of AIA rats correlated positively with reduction in the polyarthritis index. Treatment with CGP42112 inhibited the chemotaxis of AIA monocytes in vitro, possibly because of the up-regulation of AT2R expression. Intra-articular injection with CGP42112 (10 and 20 μg/kg) ameliorated the arthritis index and histological signs of arthritis. In summary, the present study strongly suggests that the up-regulation of AT2R might be an additional mechanism by which losartan exerts its therapeutic effects in AIA rats.

AB - The angiotensin II type 1 receptor (AT1R) blocker losartan ameliorates rheumatoid arthritis (RA) in an experimental model. In RA, AT2R mainly opposes AT1R, but the mechanism by which this occurs still remains obscure. In the present study, we investigated the role of AT2R in the treatment of rats with adjuvant-induced arthritis (AIA) by losartan. Adjuvant-induced arthritis rats were treated with losartan (5, 10 and 15 mg/kg) and methotrexate (MTX; 0.5 mg/kg) in vivo from day 14 to day 28. Arthritis was evaluated by the arthritis index and histological examination. Angiotensin II, tumour necrosis factor-α, and VEGF levels were examined by ELISA. The expression of AT1R and AT2R was detected by western blot and immunohistochemistry analysis. After stimulation with interleukin-1β in vitro, the effects of the AT2R agonist CGP42112 (10-8-10-5 M) on the chemotaxis of monocytes induced by 10% foetal calf serum (FCS) were analysed by using Transwell assay. Subsequently, the therapeutic effects of CGP42112 (5, 10 and 20 μg/kg) were evaluated in vivo by intra-articular injection in AIA rats. After treatment with losartan, the down-regulation of AT1R expression and up-regulation of AT2R expression in the spleen and synovium of AIA rats correlated positively with reduction in the polyarthritis index. Treatment with CGP42112 inhibited the chemotaxis of AIA monocytes in vitro, possibly because of the up-regulation of AT2R expression. Intra-articular injection with CGP42112 (10 and 20 μg/kg) ameliorated the arthritis index and histological signs of arthritis. In summary, the present study strongly suggests that the up-regulation of AT2R might be an additional mechanism by which losartan exerts its therapeutic effects in AIA rats.

KW - Adjuvant-induced arthritis

KW - Angiotensin II type 2 receptor

KW - Losartan

KW - Rheumatoid arthritis

UR - http://www.scopus.com/inward/record.url?scp=84891159115&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84891159115&partnerID=8YFLogxK

U2 - 10.1111/jcmm.12128

DO - 10.1111/jcmm.12128

M3 - Article

C2 - 24112447

AN - SCOPUS:84891159115

VL - 17

SP - 1577

EP - 1587

JO - Journal of Cellular and Molecular Medicine

JF - Journal of Cellular and Molecular Medicine

SN - 1582-1838

IS - 12

ER -