Int J Biol Sci 2024; 20(5):1707-1728. doi:10.7150/ijbs.84494 This issue Cite

Research Paper

Hspb1 protects against severe acute pancreatitis by attenuating apoptosis and ferroptosis via interacting with Anxa2 to restore the antioxidative activity of Prdx1

Jun He1, Xuyang Hou2, Junyong Wu3, Kunpeng Wang4, Xiaoyan Qi1, Zuxing Wei1, Yin Sun5, Cong Wang2, Hongliang Yao1, Kuijie Liu1✉

1. Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
2. Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
3. Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
4. Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou University, Taizhou, Zhejiang, China.
5. Institute of Pharmaceutical Pharmacology, University of South China, Hengyang, Hunan, China.

Citation:
He J, Hou X, Wu J, Wang K, Qi X, Wei Z, Sun Y, Wang C, Yao H, Liu K. Hspb1 protects against severe acute pancreatitis by attenuating apoptosis and ferroptosis via interacting with Anxa2 to restore the antioxidative activity of Prdx1. Int J Biol Sci 2024; 20(5):1707-1728. doi:10.7150/ijbs.84494. https://www.ijbs.com/v20p1707.htm
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Abstract

Graphic abstract

Acute pancreatitis (AP) is a common abdominal disease that typically resolves on its own, but the mortality rate dramatically increases when it progresses to severe acute pancreatitis (SAP). In this study, we investigated the molecular mechanism underlying the development of SAP from AP. We utilized two SAP models induced by pancreatic duct ligation and caerulein administration. Transcriptomic and proteomic analyses were subsequently performed to determine the mRNA and protein expression profiles of pancreatic samples from SAP and AP model and normal mice.

To explore the role of Hspb1 in SAP, we used Hspb1 knockout (KO) mice, a genetically engineered chronic pancreatitis strain (T7D23A), Anxa2 KO mice, and acinar cell-specific Prdx1 knockout mice. Additionally, various in vivo and in vitro assays were performed to elucidate the molecular events and direct targets of Hspb1 in acinar cells. We found that Hspb1 expression was upregulated in AP samples but significantly reduced in acinar cells from SAP samples. KO or inhibition of Hspb1 worsened AP, while AAV8-Hspb1 administration mitigated the severity of SAP and reduced remote organ damage in mice. Furthermore, AAV8-Hspb1 treatment prevented the development of chronic pancreatitis. We found that KO or inhibition of Hspb1 promoted acinar cell death through apoptosis and ferroptosis but not necroptosis or autophagy by increasing reactive oxygen species (ROS) and lipid ROS levels. Mechanistically, Hspb1 directly interacted with Anxa2 to decrease its aggregation and phosphorylation, interact with the crucial antioxidant enzyme Prdx1, and maintain its antioxidative activity by decreasing Thr-90 phosphorylation. Notably, the overexpression of Hspb1 did not have a protective effect on acinar-specific Prdx1 knockout mice.

In summary, our findings shed light on the role of Hspb1 in acinar cells. We showed that targeting Hspb1/Anxa2/Prdx1 could serve as a potential therapeutic strategy for SAP.

Keywords: Hspb1, Severe acute pancreatitis, Apoptosis, Ferroptosis, Anxa2, Prdx1


Citation styles

APA
He, J., Hou, X., Wu, J., Wang, K., Qi, X., Wei, Z., Sun, Y., Wang, C., Yao, H., Liu, K. (2024). Hspb1 protects against severe acute pancreatitis by attenuating apoptosis and ferroptosis via interacting with Anxa2 to restore the antioxidative activity of Prdx1. International Journal of Biological Sciences, 20(5), 1707-1728. https://doi.org/10.7150/ijbs.84494.

ACS
He, J.; Hou, X.; Wu, J.; Wang, K.; Qi, X.; Wei, Z.; Sun, Y.; Wang, C.; Yao, H.; Liu, K. Hspb1 protects against severe acute pancreatitis by attenuating apoptosis and ferroptosis via interacting with Anxa2 to restore the antioxidative activity of Prdx1. Int. J. Biol. Sci. 2024, 20 (5), 1707-1728. DOI: 10.7150/ijbs.84494.

NLM
He J, Hou X, Wu J, Wang K, Qi X, Wei Z, Sun Y, Wang C, Yao H, Liu K. Hspb1 protects against severe acute pancreatitis by attenuating apoptosis and ferroptosis via interacting with Anxa2 to restore the antioxidative activity of Prdx1. Int J Biol Sci 2024; 20(5):1707-1728. doi:10.7150/ijbs.84494. https://www.ijbs.com/v20p1707.htm

CSE
He J, Hou X, Wu J, Wang K, Qi X, Wei Z, Sun Y, Wang C, Yao H, Liu K. 2024. Hspb1 protects against severe acute pancreatitis by attenuating apoptosis and ferroptosis via interacting with Anxa2 to restore the antioxidative activity of Prdx1. Int J Biol Sci. 20(5):1707-1728.

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