The PI3K-AKT-mTOR signaling pathway mediates epithelial mesenchymal transition and cytoskeletal architecture changes induce to renal fibrosis after Bisphenol S exposure

Sep 30, 2026

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Bisphenol S (BPS) is increasingly used as a substitute for bisphenol A (BPA), yet the renal injury phenotype and underlying mechanism after BPS exposure remain unclear. This study tests BPS in SD rats at 50, 100, and 150 mg/kg and in HK-2 cells at 100, 200, and 400 µM, combining RNA sequencing with in vitro validation. BPS exposure disrupts cytoskeletal architecture and drives EMT in HK-2 cells, promoting renal fibrosis. PI3K-AKT-mTOR activation is identified as a key mediator, and its inhibition by Wortmannin partially reverses cytoskeletal disorders and EMT.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Background

Experimental design and model exposure

Mechanistic screening and verification

Cytoskeletal architecture, EMT, and renal fibrosis

PI3K-AKT-mTOR signaling and pharmacologic inhibition

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN The PI3K-AKT-mTOR signaling pathway mediates epithelial mesenchymal transition and cytoskeletal architecture changes induce to renal fibrosis after Bisphenol S exposure Zhaoxia Zhang1, Liming Jin2,3,4, Tao Mi2,3,4, Jinkui Wang2,3,4, Zhaoying Wang2,3,4, Junyi Luo2,3,4, Chunnian Ren2,3,4, Xin Wu2,3,4, Jiayan Liu2,3,4, Peng Guo2,3,4,5, Li Wang1􀀍 & Dawei He1􀀍 Bisphenol S (BPS) is considered a good substitute for bisphenolA (BPA) in industrial applications, and data suggest that the kidney is an important injury site after BPS exposure. However, the phenotype of kidney injury induced by BPS exposure and the mechanism of its damage remain unknown. Therefore, this study aims to investigate the phenotype and specific mechanism of kidney injury induced by BPS exposure. SD rats are treated with three different doses of BPS (50 mg/kg body weight(b.w.), 100 mg/ kg b.w., and 150 mg/ kg b.w.), and HK-2 cells are treated with 100 µM BPS, 200 µM and 400 µM BPSto mimic the in vitro and in vivo environment of BPS exposure-induced kidney injury. Meanwhile, the potential mechanism of BPS exposure-induced kidney injury was screened by RNA sequencing and further verified by in vitro experiments. BPS exposure induces cytoskeletal architecture damage and EMT transformation in HK-2 cells, promoting renal fibrosis. In addition, it was found that activation of the PI3K-AKT-mTOR signaling pathway plays a key role in cytoskeletal architecture damage and EMT transformation in HK-2, and after inhibition of PI3K-AKT-mTOR signaling by Wortmannin, the cytoskeletal architecture disorders, and EMT are partially reversed. In conclusion, we found that the activation of the PI3K-AKT-mTOR signaling pathway can mediate disturbed cytoskeletal architecture and EMT to induce renal fibrosis after BPS exposure. Keywords Bisphenol S, Cytoskeleton, EMT, Fibrosis At present, environmental pollution has seriously threatened human health. Damage from environmental pollutants, including PM2.5/microplastics/DEHP/BPA, is a current research hotspot. As a common ingredient in polycarbonate plastics and epoxy resin, bisphenol A (BPA) is one of the most productive chemical production products in the world1. It is widely used in a variety of packaging materials toys and containers and other consumer goods2,3. BPA exposure has been demonstrated to cause damage to multiple systems including reproduction, endocrine, and circulation4–6. Because of the huge health risks associated with BPA, many regulators have banned its use. Bisphenol S (BPS; 2,2–2 [4-hydroxyphenol] sulfone) is considered a good alternative to BPA 1Department of Paediatrics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400014, People’s Republic of China. 2Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing 400014, People’s Republic of China. 3Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing 400014, People’s Republic of China. 4China International Science and Technology Cooperation Base of Child Development and Critical; National Clinical Research Center for Child Health and Disorders, Chongqing; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, People’s Republic of China. 5Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou 310022, Zhejiang, People’s Republic of China. 􀀍 email: [liwang8771@126.com](liwang8771@126.com); [hedawei@hospital.cqmu.edu.cn](hedawei@hospital.cqmu.edu.cn) [www. nature.com/scientificreports/](www. nature.com/scientificreports/) in industrial applications and has gradually replaced BPA in canned and other prepackaged foods7. The ECHA conducted a market survey and found that BPS production had doubled (from 200 tons to 397 tons) between 2016 and 2017 alone8. The researchers found that BPS

FAQs

What injury process does Bisphenol S trigger in kidney-related cells?

BPS exposure induces cytoskeletal architecture damage and promotes epithelial-to-mesenchymal transition (EMT) in HK-2 cells, contributing to renal fibrosis.

How was the role of the PI3K-AKT-mTOR pathway tested?

Activation of PI3K-AKT-mTOR was assessed as a key mediator, and inhibition with Wortmannin partially reversed cytoskeletal architecture disorders and EMT.

What models and exposure levels were used to mimic BPS exposure?

SD rats received three BPS doses (50, 100, 150 mg/kg body weight), and HK-2 cells were treated with 100, 200, and 400 µM BPS to reflect in vitro and in vivo exposure conditions.

Sep 30, 2026

Uploaded by Angel