Journal: The FASEB Journal

Article Title: CBP /β‐Catenin Signaling in Hepatocytes Plays Pivotal Roles in MMP ‐7‐Mediated Liver Fibrosis in a Metabolic Dysfunction‐Associated Steatohepatitis Mouse Model

doi: 10.1096/fj.202504510R

Figure Lengend Snippet: Intrahepatic expression of MMP‐7 is markedly reduced in CBP hep‐KO mice. Male CBP hep‐KO mice (8–10 weeks old, n = 3) and P300 hep‐KO mice ( n = 3) were fed with a CDAHFD for 16 weeks. (A) Differentially expressed genes (DEGs). The volcano plot shows the results for the DEGs. (B) GOBP analysis of the top 10 downregulated genes in the livers of CBP hep‐KO mice. (C) Clustergrams of PCR array analyses of WNT/β‐catenin‐related genes (WNT/β‐catenin signaling pathway). Green indicates low expression levels, while red indicates increased expression levels. (D) MMP‐7 mRNA expression in the liver, as determined by RT‐qPCR ( n = 9, 8, and 13 per group, respectively). The results shown are representative of at least three independent experiments. Data are presented as mean ± SD. * p < 0.05; ** p < 0.01; *** p < 0.005; **** p < 0.0001, by one‐way ANOVA.

Article Snippet: The LX‐2 human hepatic stellate cell line (SCC064; Sigma‐Aldrich) was treated with recombinant human MMP‐7 (R&D Systems, 907‐MP) at concentrations ranging from 0.05–0.5 nM for 24 h prior to RNA extraction.

Techniques: Expressing, Quantitative RT-PCR

Journal: The FASEB Journal

Article Title: CBP /β‐Catenin Signaling in Hepatocytes Plays Pivotal Roles in MMP ‐7‐Mediated Liver Fibrosis in a Metabolic Dysfunction‐Associated Steatohepatitis Mouse Model

doi: 10.1096/fj.202504510R

Figure Lengend Snippet: Effects of MMP‐7 on hepatic stellate cells. (A) Schematic of the treatment protocol. HepG2 cells were treated with palmitate (200 μM, 500 μM) for 24 h. The cells were then harvested, RNA was extracted, and MMP‐7 expression was analyzed using RT‐PCR. (B) Schematic representation of the treatment protocol. After culturing LX‐2 cells for 24 h, human recombinant MMP‐7 was added at concentrations ranging from 0.05 to 0.5 nM. Cells were harvested after 24 h, RNA was extracted, and the expression of αSMA and Col1a1 was analyzed by rt‐PCR. The results are representative of at least three independent experiments. Data represent the mean ± SD. * p < 0.05; ** p < 0.01; *** p < 0.005; **** p < 0.0001, by one‐way ANOVA.

Article Snippet: The LX‐2 human hepatic stellate cell line (SCC064; Sigma‐Aldrich) was treated with recombinant human MMP‐7 (R&D Systems, 907‐MP) at concentrations ranging from 0.05–0.5 nM for 24 h prior to RNA extraction.

Techniques: Expressing, Reverse Transcription Polymerase Chain Reaction, Recombinant

Journal: The FASEB Journal

Article Title: CBP /β‐Catenin Signaling in Hepatocytes Plays Pivotal Roles in MMP ‐7‐Mediated Liver Fibrosis in a Metabolic Dysfunction‐Associated Steatohepatitis Mouse Model

doi: 10.1096/fj.202504510R

Figure Lengend Snippet: Serum MMP‐7 levels are increased in patients with MASH. (A) MMP‐7 concentrations were measured in serum samples from patients with MASH ( n = 54) and healthy volunteers ( n = 70). (B) MMP‐7 levels were measured in serum samples from patients with MASLD or MASH who underwent liver biopsy and had their fibrosis grade determined. F0 ( n = 16), F1‐2 ( n = 20), and F3‐4 ( n = 22). (C) Representative immunohistochemical images of CBP and P300 in normal ( n = 5) and NASH ( n = 6) liver biopsy specimens. Increased nuclear CBP staining was observed in hepatocytes from NASH livers. The number of cells positive for CBP and P300 in the liver was determined. For each sample, the number of positive cells was counted in five fields at 20× magnification. (D) Quantification of CBP‐positive and P300‐positive hepatocytes in liver biopsy specimens. The number of positive cells was counted in five fields at 20× magnification.

Article Snippet: The LX‐2 human hepatic stellate cell line (SCC064; Sigma‐Aldrich) was treated with recombinant human MMP‐7 (R&D Systems, 907‐MP) at concentrations ranging from 0.05–0.5 nM for 24 h prior to RNA extraction.

Techniques: Immunohistochemical staining, Staining

Journal: The FASEB Journal

Article Title: CBP /β‐Catenin Signaling in Hepatocytes Plays Pivotal Roles in MMP ‐7‐Mediated Liver Fibrosis in a Metabolic Dysfunction‐Associated Steatohepatitis Mouse Model

doi: 10.1096/fj.202504510R

Figure Lengend Snippet: Intrahepatic expression of MMP‐7 is markedly reduced in CBP hep‐KO mice. Male CBP hep‐KO mice (8–10 weeks old, n = 3) and P300 hep‐KO mice ( n = 3) were fed with a CDAHFD for 16 weeks. (A) Differentially expressed genes (DEGs). The volcano plot shows the results for the DEGs. (B) GOBP analysis of the top 10 downregulated genes in the livers of CBP hep‐KO mice. (C) Clustergrams of PCR array analyses of WNT/β‐catenin‐related genes (WNT/β‐catenin signaling pathway). Green indicates low expression levels, while red indicates increased expression levels. (D) MMP‐7 mRNA expression in the liver, as determined by RT‐qPCR ( n = 9, 8, and 13 per group, respectively). The results shown are representative of at least three independent experiments. Data are presented as mean ± SD. * p < 0.05; ** p < 0.01; *** p < 0.005; **** p < 0.0001, by one‐way ANOVA.

Article Snippet: MMP‐7 KO mice (B6.129‐ Mmp7 tm1Lmm /J, #005111) [ ] were obtained from Jackson Laboratory.

Techniques: Expressing, Quantitative RT-PCR

Journal: The FASEB Journal

Article Title: CBP /β‐Catenin Signaling in Hepatocytes Plays Pivotal Roles in MMP ‐7‐Mediated Liver Fibrosis in a Metabolic Dysfunction‐Associated Steatohepatitis Mouse Model

doi: 10.1096/fj.202504510R

Figure Lengend Snippet: Effects of MMP‐7 on hepatic stellate cells. (A) Schematic of the treatment protocol. HepG2 cells were treated with palmitate (200 μM, 500 μM) for 24 h. The cells were then harvested, RNA was extracted, and MMP‐7 expression was analyzed using RT‐PCR. (B) Schematic representation of the treatment protocol. After culturing LX‐2 cells for 24 h, human recombinant MMP‐7 was added at concentrations ranging from 0.05 to 0.5 nM. Cells were harvested after 24 h, RNA was extracted, and the expression of αSMA and Col1a1 was analyzed by rt‐PCR. The results are representative of at least three independent experiments. Data represent the mean ± SD. * p < 0.05; ** p < 0.01; *** p < 0.005; **** p < 0.0001, by one‐way ANOVA.

Article Snippet: MMP‐7 KO mice (B6.129‐ Mmp7 tm1Lmm /J, #005111) [ ] were obtained from Jackson Laboratory.

Techniques: Expressing, Reverse Transcription Polymerase Chain Reaction, Recombinant

Journal: The FASEB Journal

Article Title: CBP /β‐Catenin Signaling in Hepatocytes Plays Pivotal Roles in MMP ‐7‐Mediated Liver Fibrosis in a Metabolic Dysfunction‐Associated Steatohepatitis Mouse Model

doi: 10.1096/fj.202504510R

Figure Lengend Snippet: Serum MMP‐7 levels are increased in patients with MASH. (A) MMP‐7 concentrations were measured in serum samples from patients with MASH ( n = 54) and healthy volunteers ( n = 70). (B) MMP‐7 levels were measured in serum samples from patients with MASLD or MASH who underwent liver biopsy and had their fibrosis grade determined. F0 ( n = 16), F1‐2 ( n = 20), and F3‐4 ( n = 22). (C) Representative immunohistochemical images of CBP and P300 in normal ( n = 5) and NASH ( n = 6) liver biopsy specimens. Increased nuclear CBP staining was observed in hepatocytes from NASH livers. The number of cells positive for CBP and P300 in the liver was determined. For each sample, the number of positive cells was counted in five fields at 20× magnification. (D) Quantification of CBP‐positive and P300‐positive hepatocytes in liver biopsy specimens. The number of positive cells was counted in five fields at 20× magnification.

Article Snippet: MMP‐7 KO mice (B6.129‐ Mmp7 tm1Lmm /J, #005111) [ ] were obtained from Jackson Laboratory.

Techniques: Immunohistochemical staining, Staining

Journal: The FASEB Journal

Article Title: CBP /β‐Catenin Signaling in Hepatocytes Plays Pivotal Roles in MMP ‐7‐Mediated Liver Fibrosis in a Metabolic Dysfunction‐Associated Steatohepatitis Mouse Model

doi: 10.1096/fj.202504510R

Figure Lengend Snippet: Intrahepatic expression of MMP‐7 is markedly reduced in CBP hep‐KO mice. Male CBP hep‐KO mice (8–10 weeks old, n = 3) and P300 hep‐KO mice ( n = 3) were fed with a CDAHFD for 16 weeks. (A) Differentially expressed genes (DEGs). The volcano plot shows the results for the DEGs. (B) GOBP analysis of the top 10 downregulated genes in the livers of CBP hep‐KO mice. (C) Clustergrams of PCR array analyses of WNT/β‐catenin‐related genes (WNT/β‐catenin signaling pathway). Green indicates low expression levels, while red indicates increased expression levels. (D) MMP‐7 mRNA expression in the liver, as determined by RT‐qPCR ( n = 9, 8, and 13 per group, respectively). The results shown are representative of at least three independent experiments. Data are presented as mean ± SD. * p < 0.05; ** p < 0.01; *** p < 0.005; **** p < 0.0001, by one‐way ANOVA.

Article Snippet: Human serum MMP‐7 was measured using the Human Total MMP‐7 ELISA Kit—Quantikine (R&D Systems Inc., Minneapolis, MN, USA).

Techniques: Expressing, Quantitative RT-PCR

Journal: The FASEB Journal

Article Title: CBP /β‐Catenin Signaling in Hepatocytes Plays Pivotal Roles in MMP ‐7‐Mediated Liver Fibrosis in a Metabolic Dysfunction‐Associated Steatohepatitis Mouse Model

doi: 10.1096/fj.202504510R

Figure Lengend Snippet: Effects of MMP‐7 on hepatic stellate cells. (A) Schematic of the treatment protocol. HepG2 cells were treated with palmitate (200 μM, 500 μM) for 24 h. The cells were then harvested, RNA was extracted, and MMP‐7 expression was analyzed using RT‐PCR. (B) Schematic representation of the treatment protocol. After culturing LX‐2 cells for 24 h, human recombinant MMP‐7 was added at concentrations ranging from 0.05 to 0.5 nM. Cells were harvested after 24 h, RNA was extracted, and the expression of αSMA and Col1a1 was analyzed by rt‐PCR. The results are representative of at least three independent experiments. Data represent the mean ± SD. * p < 0.05; ** p < 0.01; *** p < 0.005; **** p < 0.0001, by one‐way ANOVA.

Article Snippet: Human serum MMP‐7 was measured using the Human Total MMP‐7 ELISA Kit—Quantikine (R&D Systems Inc., Minneapolis, MN, USA).

Techniques: Expressing, Reverse Transcription Polymerase Chain Reaction, Recombinant

Journal: The FASEB Journal

Article Title: CBP /β‐Catenin Signaling in Hepatocytes Plays Pivotal Roles in MMP ‐7‐Mediated Liver Fibrosis in a Metabolic Dysfunction‐Associated Steatohepatitis Mouse Model

doi: 10.1096/fj.202504510R

Figure Lengend Snippet: Serum MMP‐7 levels are increased in patients with MASH. (A) MMP‐7 concentrations were measured in serum samples from patients with MASH ( n = 54) and healthy volunteers ( n = 70). (B) MMP‐7 levels were measured in serum samples from patients with MASLD or MASH who underwent liver biopsy and had their fibrosis grade determined. F0 ( n = 16), F1‐2 ( n = 20), and F3‐4 ( n = 22). (C) Representative immunohistochemical images of CBP and P300 in normal ( n = 5) and NASH ( n = 6) liver biopsy specimens. Increased nuclear CBP staining was observed in hepatocytes from NASH livers. The number of cells positive for CBP and P300 in the liver was determined. For each sample, the number of positive cells was counted in five fields at 20× magnification. (D) Quantification of CBP‐positive and P300‐positive hepatocytes in liver biopsy specimens. The number of positive cells was counted in five fields at 20× magnification.

Article Snippet: Human serum MMP‐7 was measured using the Human Total MMP‐7 ELISA Kit—Quantikine (R&D Systems Inc., Minneapolis, MN, USA).

Techniques: Immunohistochemical staining, Staining