The Effect of PIN1 Inhibitor Juglone on the Spinal Cord after Acute Spinal Cord Injury (ASCI) and Its Mechanism of Action: An Animal Study on Rats

Abstract

Objective: To explore the effect and mechanism of action of PIN1 (peptidylprolylcis/transisomerase, NIMA-interacting1) inhibitor juglone (Jug) on acute spinal cord injury (ASCI) in rats. Methods: After establishing an ASCI model in Sprague-Dawley (SD) rats, Jug was administered through intraperitoneal injection ASCI+Jug group of Jug for 4 weeks. The spinal cord glial cells were extracted and identified by immunocytofluorescence. Using hematoxylin-eosin (HE) staining, the structure of rat spinal cord was examined. Tarlov scores were used to measure lower limb function and Sirius red staining was used to observe the collagen distribution in rat spinal cord. The levels of Collagen I and Collagen III in spinal cord tissue and glial cells were measured using ELISA (Enzyme linked immunosorbent assay) and the levels of PIN1, P-LKB1/LKB1 (liver kinase B1) and P-P70S6K/P70S6K (P70 ribosomaiprotein S6 kinase) were measured using Western blotting. Results: Jug improved the morphology of spinal cord tissue, and attenuated the production of TGF-β1 (transforming growth factor beta 1) and collagen in SD rats after ASCI. Furthermore, Jug can reduce Collagen I and Collagen III levels, activate LKB1 and inhibit P70S6K whether in vivo or in vitro. After overexpression of PIN1 in vitro, TGF-β1-induced collagen I and III levels were further increased. Conclusions: PIN1 inhibitor Jug can improve spinal cord tissue morphology and reduce collagen production through the LKB1/P70S6K pathway.