Platelet derived growth factor promotes the recovery of traumatic brain injury by inhibiting endoplasmic reticulum stress and autophagy-mediated pyroptosis

Fangfang Wu; Renkan Zhang; Weiyang Meng; Lei Liu; Yingdan Tang; Leilei Lu; Leilei Xia; Hongyu Zhang; Zhiguo Feng; Daqing Chen

doi:10.3389/fphar.2022.862324

Platelet derived growth factor promotes the recovery of traumatic brain injury by inhibiting endoplasmic reticulum stress and autophagy-mediated pyroptosis

Front Pharmacol. 2022 Oct 19:13:862324. doi: 10.3389/fphar.2022.862324. eCollection 2022.

Authors

Fangfang Wu¹, Renkan Zhang¹, Weiyang Meng¹, Lei Liu², Yingdan Tang¹, Leilei Lu¹, Leilei Xia³, Hongyu Zhang⁴, Zhiguo Feng^{1

4}, Daqing Chen¹

Affiliations

¹ Department of Emergency, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, China.
² The First Hospital of Jiaxing or The Affiliated Hospital of Jiaxing University, Jiaxing, China.
³ Department of Emergency, Wenzhou People's Hospital, The Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou Medical University, Wenzhou, Zhejiang, China.
⁴ School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.

Abstract

Autophagy and endoplasmic reticulum stress (ER stress) are important in numerous pathological processes in traumatic brain injury (TBI). Growing evidence has indicated that pyroptosis-associated inflammasome is involved in the pathogenesis of TBI. Platelet derived growth factor (PDGF) has been reported to be as a potential therapeutic drug for neurological diseases. However, the roles of PDGF, autophagy and ER stress in pyroptosis have not been elucidated in the TBI. This study investigated the roles of ER stress and autophagy after TBI at different time points. We found that the ER stress and autophagy after TBI were inhibited, and the expressions of pyroptosis-related proteins induced by TBI, including NLRP3, Pro-Caspase1, Caspase1, GSDMD, GSDMD P30, and IL-18, were decreased upon PDGF treatment. Moreover, the rapamycin (RAPA, an autophagy activator) and tunicamycin (TM, an ER stress activator) eliminated the PDGF effect on the pyroptosis after TBI. Interestingly, the sodium 4-phenylbutyrate (4-PBA, an ER stress inhibitor) suppressed autophagy but 3-methyladenine (3-MA, an autophagy inhibitor) not for ER stress. The results revealed that PDGF improved the functional recovery after TBI, and the effects were markedly reversed by TM and RAPA. Taken together, this study provides a new insight that PDGF is a potential therapeutic strategy for enhancing the recovery of TBI.

Keywords: PDGF; PDGF ameliorates traumatic brain injury; autophagy; er stress; pyroptosis; traumatic brain injury.