Claudin-4 induction could improve the homing and anti-fibrotic effect of bone marrow mesenchymal stem cells (BM-MSCS) in thioacetamide induced liver fibrosis in rats

Abstract

Homing and migration of bone marrow mesenchymal stem cells (BM-MSCs) to a target tissue has been a major concern because, only few cells reach the target tissue and remain there after systemic administration. The current study aimed at investigating the potential hepatoprotective role of claudin-4 in improving the homing and antifibrotic effect of BM-MSCs. In our study, Sprague-Dawley rats were randomly divided into six groups: Control group; Meloxicam group; Thioacetamide group; Thioacetamide + BM-MSCs group; Meloxicam + Thioacetamide group; Thioacetamide + Meloxicam + BM-MSCs. Flowcytometry, Western Blot, hematoxylin and eosin (H&E), Masson’s trichrome staining, immunohistochemical studies for the detection of α-Smooth muscle actin (α-SMA) and enzyme-linked immunosorbent assay (ELISA) were involved to measure different parameters. Results showed that in vivo BM-MSCs administration significantly improved histopathological changes and attenuated the elevated liver enzymes, lipid peroxidation marker malondialdehyde (MDA), inflammatory cytokine levels including tumor necrosis factor alpha (TNF-α), cyclooxygenase 2 enzyme (COX-2) enzyme, nuclear factor kappaB (NF-κB) and both hydroxyproline content and α-SMA were also reduced. Additionally, there was an increase in the activity of reduced glutathione (GSH) in liver tissue. Moreover, the PKH26 staining showed that meloxicam which induced the expression of claudin-4 resulted in more homing of BM-MSCs to the liver more than those without meloxicam addition. In conclusion, the present study demonstrated improved homing and anti-fibrotic effect of BM-MSCs, which is thought to be partly mediated by the overexpression of claudin-4 by meloxicam.