Expression and significance of irisin in rats model with adenine-induced chronic kidney disease_West China Medical Journal

Authors：

XIA Qingling ^1,2 , LI Yan ^1,2 , KANG Ting ^1,2 , ZHU Tingting ^1,2 , WU Weihua ^1,2 ,  OU Santao ^1,2

1. Department of Nephrology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P. R. China;
2. Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan 646000, P. R. China;

Corresponding author：

OU Santao, Email: ousantao@163.com

Keywords：

Chronic kidney disease; renal fibrosis; irisin

DOI：

10.7507/1002-0179.202308009

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To explore the expression and changes of serum irisin in adenine-induced chronic kidney disease (CKD) model, and the role of irisin and related pathway in CKD renal fibrosis. Methods Twenty male SD rats were randomly divided into a control group and a model group (CKD group) using a simple randomization method, with 10 rats in each group. At the end of the 2nd and 4th week, biochemical indicators, serum irisin and serum bone morphogenetic protein 7 (BMP7) levels, renal pathologic changes and interstitial fibrosis of renal tubules were measured in two groups of rats. The protein expression levels and messenger RNA (mRNA) expression levels of alpha-smooth muscle actin (α-SMA), collagen type I (Col-Ⅰ), BMP7, and Smad1 in rat kidney tissue were detected and compared. Results Compared with the control group at the end of the 2nd and 4th week, the CKD group showed that the serum creatinine (Scr), serum urea nitrogen (BUN), and 24-hour urinary protein level were increased (P<0.05), the protein expression levels and mRNA expression levels of α-SMA and Col-Ⅰ were increased (P<0.05), while the serum irisin and serum BMP7 were decreased (P<0.05), the protein expression levels and mRNA expression levels of BMP7 and Smad1 were reduced (P<0.05). Compared with the end of the 2nd week, the CKD group at the end of the 4th week showed that the serum Scr, serum BUN, and 24-hour urinary protein level were increased (P<0.05), the protein expression levels and mRNA expression levels of α-SMA and Col-Ⅰ were increased (P<0.05), while the serum irisin and serum BMP7 were decreased (P<0.05), the protein expression levels and mRNA expression levels of BMP7 and Smad1 were reduced (P<0.05). Compared to the control group, the renal tissue structure of the CKD group showed significant structural disorders and interstitial fibrosis of the renal tissue, which worsened over time. Serum irisin was negatively correlated with α- SMA and Col - Ⅰ (r=−0.917, −0.902, P<0.001) respectively, while serum irisin was positively correlated with serum BMP7 (r=0.842, P<0.001); Kidney tissue BMP7 was positively correlated with Smad1 (r=0.884, P<0.001). The cluster heat map showed that compared with the control group, BMP7 and recombinant fibronectin type Ⅲ domain containing were significantly decreased, α-SMA and Col-Ⅰ were significantly increased in CKD group; recombinant fibronectin type Ⅲ domain containing were positively correlated with BMP7, and negatively correlated with α-SMA and Col-Ⅰ. Conclusions irisin may be involved in the process of renal fibrosis in adenine-induced CKD via the BMP7/Smad1 axis. This will provide new ideas for the prevention and treatment of renal fibrosis.

Citation： XIA Qingling, LI Yan, KANG Ting, ZHU Tingting, WU Weihua, OU Santao. Expression and significance of irisin in rats model with adenine-induced chronic kidney disease. West China Medical Journal, 2024, 39(2): 268-274. doi: 10.7507/1002-0179.202308009 Copy

1.	唐露, 司晶, 徐寒梅. 肾纤维化相关信号通路研究进展. 药学进展, 2021, 45(7): 532-538.
2.	陈婷, 黄文辉, 许丽丽, 等. 鸢尾素在急性肾损伤中的研究进展. 华西医学, 2023, 38(1): 116-120.
3.	Do DV, Park SY, Nguyen GT, et al. The effects of irisin on the interaction between hepatic stellate cell and macrophage in liver fibrosis. Endocrinol Metab (Seoul), 2022, 37(4): 620-629.
4.	Liao X, Zhan W, Li R, et al. Irisin ameliorates endoplasmic reticulum stress and liver fibrosis through inhibiting PERK-mediated destabilization of HNRNPA1 in hepatic stellate cells. Biol Chem, 2021, 402(6): 703-715.
5.	Ren Y, Zhang J, Wang M, et al. Identification of irisin as a therapeutic agent that inhibits oxidative stress and fibrosis in a murine model of chronic pancreatitis. Biomed Pharmacother, 2020, 126: 110101.
6.	Peng H, Wang Q, Lou T, et al. Myokine mediated muscle-kidney crosstalk suppresses metabolic reprogramming and fibrosis in damaged kidneys. Nat Commun, 2017, 8(1): 1493.
7.	Lund RJ, Davies MR, Hruska KA. Bone morphogenetic protein-7: an anti-fibrotic morphogenetic protein with therapeutic importance in renal disease. Curr Opin Nephrol Hypertens, 2002, 11(1): 31-36.
8.	Lv W, Booz GW, Wang Y, et al. Inflammation and renal fibrosis: recent developments on key signaling molecules as potential therapeutic targets. Eur J Pharmacol, 2018, 820: 65-76.
9.	Huang R, Fu P, Ma L. Kidney fibrosis: from mechanisms to therapeutic medicines. Signal Transduct Target Ther, 2023, 8(1): 129.
10.	敬雪明, 张诗琬, 喻雪琴, 等. 信号通路在肾纤维化发生机制中作用的研究进展. 山东医药, 2020, 60(2): 102-105.
11.	Diwan V, Brown L, Gobe GC. Adenine-induced chronic kidney disease in rats. Nephrology (Carlton), 2018, 23(1): 5-11.
12.	Gan W, Chen W, Li T, et al. Circulating irisin level in chronic kidney disease patients: a systematic review and meta-analysis. Int Urol Nephrol, 2022, 54(6): 1295-1302.
13.	赵丽华, 高宇. 鸢尾素在糖脂代谢相关疾病中的研究进展. 中国动脉硬化杂志, 2023, 31(8): 731-736.
14.	Zhang J, Bi J, Ren Y, et al. Involvement of GPX4 in irisin’s protection against ischemia reperfusion-induced acute kidney injury. J Cell Physiol, 2021, 236(2): 931-945.
15.	Jiang S, Oh DS, Dorotea D, et al. Dojuksan ameliorates tubulointerstitial fibrosis through irisin-mediated muscle-kidney crosstalk. Phytomedicine, 2021, 80: 153393.
16.	Kim S, Jeong CH, Song SH, et al. Micellized protein transduction domain-bone morphogenetic protein-7 efficiently blocks renal fibrosis via inhibition of transforming growth factor-beta-mediated epithelial-mesenchymal transition. Front Pharmacol, 2020, 11: 591275.
17.	Li RX, Yiu WH, Tang SC. Role of bone morphogenetic protein-7 in renal fibrosis. Front Physiol, 2015, 6: 114.
18.	Peng W, Zhou X, Xu T, et al. BMP-7 ameliorates partial epithelial-mesenchymal transition by restoring SnoN protein level via Smad1/5 pathway in diabetic kidney disease. Cell Death Dis, 2022, 13(3): 254.
19.	Ruiqi L, Ming P, Qihang S, et al. Saikosaponin D inhibits peritoneal fibrosis in rats with renal failure by regulation of TGFβ1/BMP7/Gremlin1/Smad pathway. Front Pharmacol, 2021, 12: 628671.
20.	Manson SR, Song JB, Hruska KA, et al. HDAC dependent transcriptional repression of Bmp-7 potentiates TGF-β mediated renal fibrosis in obstructive uropathy. J Urol, 2014, 191(1): 242-252.

1. 唐露, 司晶, 徐寒梅. 肾纤维化相关信号通路研究进展. 药学进展, 2021, 45(7): 532-538.
2. 陈婷, 黄文辉, 许丽丽, 等. 鸢尾素在急性肾损伤中的研究进展. 华西医学, 2023, 38(1): 116-120.
3. Do DV, Park SY, Nguyen GT, et al. The effects of irisin on the interaction between hepatic stellate cell and macrophage in liver fibrosis. Endocrinol Metab (Seoul), 2022, 37(4): 620-629.
4. Liao X, Zhan W, Li R, et al. Irisin ameliorates endoplasmic reticulum stress and liver fibrosis through inhibiting PERK-mediated destabilization of HNRNPA1 in hepatic stellate cells. Biol Chem, 2021, 402(6): 703-715.
5. Ren Y, Zhang J, Wang M, et al. Identification of irisin as a therapeutic agent that inhibits oxidative stress and fibrosis in a murine model of chronic pancreatitis. Biomed Pharmacother, 2020, 126: 110101.
6. Peng H, Wang Q, Lou T, et al. Myokine mediated muscle-kidney crosstalk suppresses metabolic reprogramming and fibrosis in damaged kidneys. Nat Commun, 2017, 8(1): 1493.
7. Lund RJ, Davies MR, Hruska KA. Bone morphogenetic protein-7: an anti-fibrotic morphogenetic protein with therapeutic importance in renal disease. Curr Opin Nephrol Hypertens, 2002, 11(1): 31-36.
8. Lv W, Booz GW, Wang Y, et al. Inflammation and renal fibrosis: recent developments on key signaling molecules as potential therapeutic targets. Eur J Pharmacol, 2018, 820: 65-76.
9. Huang R, Fu P, Ma L. Kidney fibrosis: from mechanisms to therapeutic medicines. Signal Transduct Target Ther, 2023, 8(1): 129.
10. 敬雪明, 张诗琬, 喻雪琴, 等. 信号通路在肾纤维化发生机制中作用的研究进展. 山东医药, 2020, 60(2): 102-105.
11. Diwan V, Brown L, Gobe GC. Adenine-induced chronic kidney disease in rats. Nephrology (Carlton), 2018, 23(1): 5-11.
12. Gan W, Chen W, Li T, et al. Circulating irisin level in chronic kidney disease patients: a systematic review and meta-analysis. Int Urol Nephrol, 2022, 54(6): 1295-1302.
13. 赵丽华, 高宇. 鸢尾素在糖脂代谢相关疾病中的研究进展. 中国动脉硬化杂志, 2023, 31(8): 731-736.
14. Zhang J, Bi J, Ren Y, et al. Involvement of GPX4 in irisin’s protection against ischemia reperfusion-induced acute kidney injury. J Cell Physiol, 2021, 236(2): 931-945.
15. Jiang S, Oh DS, Dorotea D, et al. Dojuksan ameliorates tubulointerstitial fibrosis through irisin-mediated muscle-kidney crosstalk. Phytomedicine, 2021, 80: 153393.
16. Kim S, Jeong CH, Song SH, et al. Micellized protein transduction domain-bone morphogenetic protein-7 efficiently blocks renal fibrosis via inhibition of transforming growth factor-beta-mediated epithelial-mesenchymal transition. Front Pharmacol, 2020, 11: 591275.
17. Li RX, Yiu WH, Tang SC. Role of bone morphogenetic protein-7 in renal fibrosis. Front Physiol, 2015, 6: 114.
18. Peng W, Zhou X, Xu T, et al. BMP-7 ameliorates partial epithelial-mesenchymal transition by restoring SnoN protein level via Smad1/5 pathway in diabetic kidney disease. Cell Death Dis, 2022, 13(3): 254.
19. Ruiqi L, Ming P, Qihang S, et al. Saikosaponin D inhibits peritoneal fibrosis in rats with renal failure by regulation of TGFβ1/BMP7/Gremlin1/Smad pathway. Front Pharmacol, 2021, 12: 628671.
20. Manson SR, Song JB, Hruska KA, et al. HDAC dependent transcriptional repression of Bmp-7 potentiates TGF-β mediated renal fibrosis in obstructive uropathy. J Urol, 2014, 191(1): 242-252.

West China Medical Journal

Expression and significance of irisin in rats model with adenine-induced chronic kidney disease

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content