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Protective Effects of Baicalin on Diabetes Mellitus-Induced Renal Fibrosis in Mice

50 Pages Posted: 4 Jan 2019

See all articles by Xiao-Tan Zhang

Xiao-Tan Zhang

Jinan University

Guang Wang

Jinan University

Liu-fang Ye

Jinan University

Yu Pu

Jinan University

Run-tong Li

Jinan University

Jianxin Liang

Jinan University

Lijun Wang

Jinan University

Kenneth Ka Ho Lee

The Chinese University of Hong Kong (CUHK)

Xuesong Yang

Jinan University - International Joint Laboratory for Embryonic Development & Prenatal Medicine; Jinan University - Key Laboratory for Regenerative Medicine of the Ministry of Education

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Abstract

Baicalin is a flavone glycoside that possess numerous pharmacological properties including anti-inflammatory, anti-cancer and anti-pruritic effects. Based on these properties, we investigated whether baicalin could be used to alleviate kidney fibrosis induced by diabetes mellitus. Using a streptozotocin (STZ)-induced diabetic mouse model, we found that baicalin treatment could suppress diabetes-enhanced water consumption, urine volume production, blood urea nitrogen (BUN), serum creatinine and urinary albumin/urinary creatinine (UACR). Correspondingly, baicalin treatment could significantly maintain the morphology of the glomerulus and renal tubules in diabetes-induced kidney lesions by repressing WT1 and Nephrin expressions in the glomeruli, as well as LTL, caspases-9 and Fas expressions in the renal tubules. We also determined that baicalin could suppress inflammation responses and reduced MDA activities that were enhnaced by diabetes while increasing SOD, CAT, GPX and Nrf2 expressions that were inversely lowered. We demonstrated the presence of interstitial fibrosis in the diabetic kidney but this could be alleviated by baicalin which downregulated ɑ-SMA and TGF-β1 expressiond (key pro-fibrotic markers). We investigated Klotho a transmembrane protein that is expressed by renal tubule epithelial cells. Secreted form of Klotho could bind to TGF-β1 receptors and block the TGFβ1 signaling pathway. We determined that hypermethylation of the Klotho promoter plays an important role in baicalin's ability to rescue renal fibrosis induced by diabetes mellitus. In sum, our results showed that baicalin could alleviate renal fibrosis-induced by diabetes through partly modulating Klotho promoter methylation.

Funding Statement: This study was supported by NSFC grant (31771331, 81741016), Science and Technology Planning Project of Guangdong Province (2017A050506029, 2017A020214015, 2016B030229002), Science and Technology Program of Guangzhou (201710010054), Guangdong Natural Science Foundation (2016A030311044), Project of National University Students "Challenge Cup" (18112003).

Declaration of Interests: The authors declare that there are no competing financial interests.

Ethics Approval Statement: This study was carried out in strict accordance with the recommendations of the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Animal Ethic Committee at Jinan University.

Keywords: Diabetes; Renal fibrosis; Klotho; TGF-β1; Baicalin

Suggested Citation

Zhang, Xiao-Tan and Wang, Guang and Ye, Liu-fang and Pu, Yu and Li, Run-tong and Liang, Jianxin and Wang, Lijun and Ka Ho Lee, Kenneth and Yang, Xuesong, Protective Effects of Baicalin on Diabetes Mellitus-Induced Renal Fibrosis in Mice (December 29, 2018). Available at SSRN: https://ssrn.com/abstract=3309387 or http://dx.doi.org/10.2139/ssrn.3309387

Xiao-Tan Zhang

Jinan University

Huang Pu Da Dao Xi 601, Tian He District
Guangzhou, Guangdong 510632
China

Guang Wang

Jinan University

Huang Pu Da Dao Xi 601, Tian He District
Guangzhou, Guangdong 510632
China

Liu-fang Ye

Jinan University

Huang Pu Da Dao Xi 601, Tian He District
Guangzhou, Guangdong 510632
China

Yu Pu

Jinan University

Huang Pu Da Dao Xi 601, Tian He District
Guangzhou, Guangdong 510632
China

Run-tong Li

Jinan University

Huang Pu Da Dao Xi 601, Tian He District
Guangzhou, Guangdong 510632
China

Jianxin Liang

Jinan University

Huang Pu Da Dao Xi 601, Tian He District
Guangzhou, Guangdong 510632
China

Lijun Wang

Jinan University

Huang Pu Da Dao Xi 601, Tian He District
Guangzhou, Guangdong 510632
China

Kenneth Ka Ho Lee

The Chinese University of Hong Kong (CUHK)

Shatin, N.T.
Hong Kong
Hong Kong

Xuesong Yang (Contact Author)

Jinan University - International Joint Laboratory for Embryonic Development & Prenatal Medicine ( email )

Guangzhou, 510632
China

Jinan University - Key Laboratory for Regenerative Medicine of the Ministry of Education ( email )

Guangzhou, 510632
China

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