Vol. 5, Issue 4, Part C (2019)

Abstract
Homing and migration of 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 (CLDN-4) in improving the homing and anti-fibrotic effect of BM-MSCs. In our study, Sprague-Dawley rats were randomly divided into six groups: Control group; Forskolin (FSK) group; Thioacetamide (TAA) group; FSK+TAA group; TAA+BM-MSCs group; FSK+TAA+ 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 combination of FSK added to BM-MSCs significantly improved histopathological changes and attenuated the elevated liver enzymes, hydroxyproline content, oxidative stress markers, inflammatory cytokine levels including tumor necrosis factor alpha (TNF-α), tumor growth factor beta (TGF-α1), interleukin-1 beta (IL-α1), cyclooxygenase 2 enzyme (COX-2) enzyme, transcription factor nuclear factor kappa B (NF-κB) and α-SMA were also reduced. Moreover, the PKH26 staining showed that FSK added to BM-MSCs resulted in more homing of BM-MSCs to the liver more than those without FSK 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 modulation of CLDN-4.