JHP-7 (QLLEELKR), a heptapeptide derived from Jinhua ham, may ameliorate intrauterine adhesion (IUA) via inhibiting inflammatory response and apoptosis

Objective

This study aimed to investigate the effect of JHP-7(QLLEELKR) derived from Jinhua ham on IUA, in order to provide new methods and new ideas for the clinical treatment of IUA.

Methods

The JHP-7 was synthesized by solid-phase peptide synthesis (SPPS). An in vitro model (human endometrial epithelial cells (HEECs) induced by 10 ng/mL TGF-β1) and an in vivo model (C57BL/6 mice induced by mechanical curettage and LPS stimulation) were used in the study. In vitro, HEEC were co-cultured with TGF-β1with or without JHP-7 (1 μM and 10 μM) for 48 h, followed by RT-qPCR and Western blotting analysis. Meanwhile, the fluorescent ROS probe was employed to assess oxidative stress levels. In vivo, IUA mice were preventively treated with JHP-7 (150 μg/kg/d and 300 μg/kg/d) for 14 days, after which uterine tissues were collected for histopathological evaluation using H&E and Masson staining, as well as molecular analysis via RT-qPCR and Western blotting to measure mRNA and protein expression levels.

Results

In vitro, JHP-7 significantly inhibited the expression of proinflammatory and fibrosis markers, reduced the ROS, and protected endometrial function. Further studies showed that JHP-7 inhibited the apoptosis of TGF-β1-induced HEECs, and reduced the expression of TLR4, p-NF-κB, and p-MAPK. In vivo, JHP-7 significantly improved the uterine morphology and reduced collagen deposition in IUA mice. Reduced expression of TLR4, MyD88, p-NF-κB, p-MAPK and up-regulating expression of Bcl2 were also detected after JHP-7 treatment.

Conclusion

JHP-7 could ameliorate IUA via inhibiting inflammation and apoptosis, which may be related to the TLR4/MyD88/MAPK/NF-κB signaling pathway.