C-X-C Chemokine Receptor Type 4 (CXCR-4) Functionally-Selective Allosteric Agonist ATI2341 Promotes the Recovery of Uterosacral Ligament

Abstract

This study intends to assess whether CXCR4 functionally-selective allosteric agonist ATI2341 recovers uterosacral ligament. The 50 female rats were assigned into five groups including A group (normal healthy rats), B group (rats with uterine ligament injury), C group (injury rats treated with UC-MSCs cells), D group (treated with ATI2341); E group (treated with UC-MSCs cells and ATI2341) followed by analysis of uterus pathological changes by H&E staining and the expression of CD44, CD90, CXCR4, and SDF-1 by Western Blot or PT-PCR. There was regular and pyknotic fibrillar connective tissue and few small vessels in A group without infiltration of inflammatory cells. However, B group showed infiltration of inflammatory cells with few fibroblasts of fibrous tissue. The quantity of infiltration of inflammatory cells in C group and D group was less than that in B group with few visible new-born vessels. The improvement of pathological condition in uterus tissue in E group was the most among treatment groups. The number of wavy fiber was increased gradually and fibrillar connective tissue was changed into dense with elevated new-born vessels in ligament. The expression CD44, CD90, CXCR4 and SDF-1 was upregulated effectively by ATI2341. In conclusion, ATI2341 can upregulate the expression of CD44, CD90, CXCR4 and SDF-1 and promote the recovery of uterine ligament in rats, indicating that it might be a new approach for the treatment of uterine ligament.