| Autor: |
Hiroshi Yokoyama, Takahiro Masaki, Ikuyo Inoue, Mariko Nakamura, Yoshihiro Mezaki, Chisato Saeki, Tsunekazu Oikawa, Masayuki Saruta, Hiroyuki Takahashi, Masahiro Ikegami, Hiroshi Hano, Kenichi Ikejima, Soichi Kojima, Tomokazu Matsuura |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Heliyon, Vol 5, Iss 2, Pp e01231- (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2405-8440 |
| DOI: |
10.1016/j.heliyon.2019.e01231 |
| Popis: |
Transforming growth factor-β (TGF-β) is a key driver for liver fibrogenesis. TGF-β must be activated in order to function. Plasma kallikrein (PLK) is a TGF-β activator that cleaves the latency-associated protein (LAP) between arginine58 and lysine59 residues and releases active TGF-β from the latent TGF-β-LAP complex. Thus, the generation of two LAP degradation products, ending at arginine58 (R58/LAP-DPs) and beginning from lysine59 (L59/LAP-DPs), reflects PLK-dependent TGF-β activation. However, the significance and details of TGF-β activation in patients with chronic liver disease (CLD) remain uncertain. We herein examined the PLK-dependent TGF-β activation in patients by detecting R58 and L59/LAP-DPs. A total of 234 patients with CLD were included in this study. Liver biopsy specimens were used for immunostaining to detect R58/LAP-DPs, while plasma samples were subjected to an enzyme-linked immunosorbent assay to measure the L59/LAP-DP concentration. R58/LAP-DP was robustly expressed in and around the sinusoidal cells before the development of the fibrous regions. The R58/LAP-DP expression at fibrosis stage 1 was higher than at any other stages, and the relationship between the plasma L59/LAP-DP level and the stage of fibrosis also showed a similar trend. The abundance of plasma L59/LAP-DP showed no correlation with the levels of direct serum biomarkers of liver fibrosis; however, its changes during interferon-based therapy for chronic hepatitis C were significantly associated with virological responses. Our results suggest that PLK-dependent TGF-β activation occurs in the early stages of fibrosis and that its unique surrogate markers, R58 and L59/LAP-DPs, are useful for monitoring the clinical course of CLD. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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