PMID- 27140333 OWN - NLM STAT- MEDLINE DCOM- 20170303 LR - 20220410 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 155 DP - 2016 Jun 15 TI - Non-canonical role of matrix metalloprotease (MMP) in activation and migration of hepatic stellate cells (HSCs). PG - 155-60 LID - S0024-3205(16)30251-X [pii] LID - 10.1016/j.lfs.2016.04.031 [doi] AB - AIMS: Matrix metalloproteinases (MMPs) that degrade extracellular matrix (ECM) and help to resolve the excess matrix are considered to be under-expressed in fibrosis. MMPs are generally anti-fibrotic, however others can have pro-fibrotic functions. Therefore, the aim of this study was to find out the mechanism of pro-fibrotic function of MMPs in hepatic stellate cells' (HSC's) activation and migration. MAIN METHODS: Human MMP Antibody Array from Abcam was used to profile MMPs in macrophages. Gelatin or casein zymography was performed using 10% SDS-polyacrylamide gels (SDS-PAGE) containing gelatin (1mg/ml) or Casein (1mg/ml) as substrate. HSCs migration assay was performed using Boyden chamber as described previously (Guo et al., 2007, McGarrigle et al., 2006, Shan et al., 2006 and Yang and Huang, 2005). Real-time PCR with SYBR green was performed using iTaq universal SYBR(R) Green supermix (BIO-RAD) and a 7500 Real-Time PCR System (Applied Biosystems). Collagen, type I, alpha 1 (COL1A1), alpha smooth muscle actin (alpha-SMA) expression was determined by immunoblot analysis. KEY FINDINGS: We first profiled the expression of all MMPs in primary murine bone marrow-derived macrophages (BMDMs) and differentiated THP-1 cells and found that MMP-8, -10, & -13, were significantly overexpressed after 12h of lipopolysaccharide (LPS) treatment. Based on this pattern of expression, we speculated that macrophage MMP-8,-10, &-13 might play a non-canonical role in HSCs activation. Further, we found that exogenous active MMP-8 (Collagenase-2) treated HSC shows markedly increased migration and COL1A1 expression as compared to MMP-10 and MMP-13 treated HSCs. Thus, macrophage MMP-8 (Collagenase-2) expression in macrophages emerges as an important moderator of HSC cell migration and invasion. SIGNIFICANCE: These findings suggest that macrophage MMP-8 promotes HSC activation and might have a role in liver disease progression. MMP-8 targeting in the liver may have therapeutic potential in alcoholic liver disease (ALD). CI - Copyright (c) 2016 Elsevier Inc. All rights reserved. FAU - Baig, Mirza S AU - Baig MS AD - Center for Biosciences and Biomedical Engineering (BSBE), Indian Institute of Technology Indore (IITI), Indore, MP, India; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. Electronic address: msb@iiti.ac.in. FAU - Yaqoob, Usman AU - Yaqoob U AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. FAU - Cao, Sheng AU - Cao S AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. FAU - Saqib, Uzma AU - Saqib U AD - Discipline of Chemistry, School of Basic Sciences, Indian Institute of Technology Indore (IITI), Indore, MP, India. FAU - Shah, Vijay H AU - Shah VH AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. Electronic address: Shah.Vijay@mayo.edu. LA - eng PT - Journal Article DEP - 20160429 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - EC 3.4.24.- (Matrix Metalloproteinases) SB - IM MH - Animals MH - Cell Line MH - *Cell Movement MH - Female MH - Hepatic Stellate Cells/cytology/*enzymology MH - Humans MH - Matrix Metalloproteinases/*metabolism MH - Mice MH - Mice, Inbred C57BL OTO - NOTNLM OT - Alpha-SMA OT - Collagen I OT - Fibrosis OT - Macrophage OT - Matrix metalloproteinase (MMP) EDAT- 2016/05/04 06:00 MHDA- 2017/03/04 06:00 CRDT- 2016/05/04 06:00 PHST- 2016/03/29 00:00 [received] PHST- 2016/04/22 00:00 [revised] PHST- 2016/04/24 00:00 [accepted] PHST- 2016/05/04 06:00 [entrez] PHST- 2016/05/04 06:00 [pubmed] PHST- 2017/03/04 06:00 [medline] AID - S0024-3205(16)30251-X [pii] AID - 10.1016/j.lfs.2016.04.031 [doi] PST - ppublish SO - Life Sci. 2016 Jun 15;155:155-60. doi: 10.1016/j.lfs.2016.04.031. Epub 2016 Apr 29.