Expression patterns of STAT3, ERK and estrogen-receptor α are associated with development and histologic severity of hepatic steatosis: a retrospective study
Abstract Background Hepatic steatosis renders hepatocytes vulnerable to injury, resulting in the progression of preexisting liver disease. Previous animal and cell culture studies implicated mammalian target of rapamycin (mTOR), signal transducer and activator of transcription-3 (STAT3), extracellul...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-04-01
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| Series: | Diagnostic Pathology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13000-018-0698-8 |
| _version_ | 1818307294813749248 |
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| author | Euno Choi Won Kim Sae Kyung Joo Sunyoung Park Jeong Hwan Park Yun Kyung Kang So-Young Jin Mee Soo Chang |
| author_facet | Euno Choi Won Kim Sae Kyung Joo Sunyoung Park Jeong Hwan Park Yun Kyung Kang So-Young Jin Mee Soo Chang |
| author_sort | Euno Choi |
| collection | DOAJ |
| description | Abstract Background Hepatic steatosis renders hepatocytes vulnerable to injury, resulting in the progression of preexisting liver disease. Previous animal and cell culture studies implicated mammalian target of rapamycin (mTOR), signal transducer and activator of transcription-3 (STAT3), extracellular signal-regulated kinase (ERK) and estrogen-receptor α in the pathogenesis of hepatic steatosis and disease progression. However, to date there have been few studies performed using human liver tissue to study hepatic steatosis. We examined the expression patterns of mTOR, STAT3, ERK and estrogen-receptor α in liver tissues from patients diagnosed with hepatic steatosis. Methods We reviewed the clinical and histomorphological features of 29 patients diagnosed with hepatic steatosis: 18 with non-alcoholic fatty liver disease (NAFLD), 11 with alcoholic fatty acid disease (AFLD), and a control group (16 biliary cysts and 22 hepatolithiasis). Immunohistochemistry was performed on liver tissue using an automated immunostainer. The histologic severity of hepatic steatosis was evaluated by assessing four key histomorphologic parameters common to NAFLD and AFLD: steatosis, lobular inflammation, ballooning degeneration and fibrosis. Results mTOR, phosphorylated STAT3, phosphorylated pERK, estrogen-receptor α were found to be more frequently expressed in the hepatic steatosis group than in the control group. Specifically, mTOR was expressed in 78% of hepatocytes, and ERK in 100% of hepatic stellate cells, respectively, in patients with NAFLD. Interestingly, estrogen-receptor α was diffusely expressed in hepatocytes in all NALFD cases. Phosphorylated (active) STAT3 was expressed in 73% of hepatocytes and 45% of hepatic stellate cells in patients with AFLD, and phosphorylated (active) ERK was expressed in hepatic stellate cells in all AFLD cases. Estrogen-receptor α was expressed in all AFLD cases (focally in 64% of AFLD cases, and diffusely in 36%). Phosphorylated STAT3 expression in hepatocytes and hepatic stellate cells correlated with severe lobular inflammation, severe ballooning degeneration and advanced fibrosis, whereas diffusely expressed estrogen-receptor α correlated with a mild stage of fibrosis. Conclusions Our data indicate ERK activation and estrogen-receptor α may be relevant in the development of hepatic steatosis. However, diffuse expression of estrogen-receptor α would appear to impede disease progression, including hepatic fibrosis. Finally, phosphorylated STAT3 may also contribute to disease progression. |
| first_indexed | 2024-12-13T06:56:06Z |
| format | Article |
| id | doaj.art-592f2a1f748f4585969c1067f93f0680 |
| institution | Directory Open Access Journal |
| issn | 1746-1596 |
| language | English |
| last_indexed | 2024-12-13T06:56:06Z |
| publishDate | 2018-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Diagnostic Pathology |
| spelling | doaj.art-592f2a1f748f4585969c1067f93f06802022-12-21T23:56:01ZengBMCDiagnostic Pathology1746-15962018-04-011311910.1186/s13000-018-0698-8Expression patterns of STAT3, ERK and estrogen-receptor α are associated with development and histologic severity of hepatic steatosis: a retrospective studyEuno Choi0Won Kim1Sae Kyung Joo2Sunyoung Park3Jeong Hwan Park4Yun Kyung Kang5So-Young Jin6Mee Soo Chang7Department of Pathology, Seoul National University Boramae Hospital, Seoul National University College of MedicineDepartment of Internal Medicine, Seoul National University Boramae Hospital, Seoul National University College of MedicineDepartment of Internal Medicine, Seoul National University Boramae Hospital, Seoul National University College of MedicineDepartment of Pathology, Seoul National University Boramae Hospital, Seoul National University College of MedicineDepartment of Pathology, Seoul National University Boramae Hospital, Seoul National University College of MedicineDepartment of Pathology, Seoul Paik Hospital, Inje University College of MedicineDepartment of Pathology, Soon Chun Hyang University HospitalDepartment of Pathology, Seoul National University Boramae Hospital, Seoul National University College of MedicineAbstract Background Hepatic steatosis renders hepatocytes vulnerable to injury, resulting in the progression of preexisting liver disease. Previous animal and cell culture studies implicated mammalian target of rapamycin (mTOR), signal transducer and activator of transcription-3 (STAT3), extracellular signal-regulated kinase (ERK) and estrogen-receptor α in the pathogenesis of hepatic steatosis and disease progression. However, to date there have been few studies performed using human liver tissue to study hepatic steatosis. We examined the expression patterns of mTOR, STAT3, ERK and estrogen-receptor α in liver tissues from patients diagnosed with hepatic steatosis. Methods We reviewed the clinical and histomorphological features of 29 patients diagnosed with hepatic steatosis: 18 with non-alcoholic fatty liver disease (NAFLD), 11 with alcoholic fatty acid disease (AFLD), and a control group (16 biliary cysts and 22 hepatolithiasis). Immunohistochemistry was performed on liver tissue using an automated immunostainer. The histologic severity of hepatic steatosis was evaluated by assessing four key histomorphologic parameters common to NAFLD and AFLD: steatosis, lobular inflammation, ballooning degeneration and fibrosis. Results mTOR, phosphorylated STAT3, phosphorylated pERK, estrogen-receptor α were found to be more frequently expressed in the hepatic steatosis group than in the control group. Specifically, mTOR was expressed in 78% of hepatocytes, and ERK in 100% of hepatic stellate cells, respectively, in patients with NAFLD. Interestingly, estrogen-receptor α was diffusely expressed in hepatocytes in all NALFD cases. Phosphorylated (active) STAT3 was expressed in 73% of hepatocytes and 45% of hepatic stellate cells in patients with AFLD, and phosphorylated (active) ERK was expressed in hepatic stellate cells in all AFLD cases. Estrogen-receptor α was expressed in all AFLD cases (focally in 64% of AFLD cases, and diffusely in 36%). Phosphorylated STAT3 expression in hepatocytes and hepatic stellate cells correlated with severe lobular inflammation, severe ballooning degeneration and advanced fibrosis, whereas diffusely expressed estrogen-receptor α correlated with a mild stage of fibrosis. Conclusions Our data indicate ERK activation and estrogen-receptor α may be relevant in the development of hepatic steatosis. However, diffuse expression of estrogen-receptor α would appear to impede disease progression, including hepatic fibrosis. Finally, phosphorylated STAT3 may also contribute to disease progression.http://link.springer.com/article/10.1186/s13000-018-0698-8Hepatic steatosisNon-alcoholicAlcoholicmTORpSTAT3pERK |
| spellingShingle | Euno Choi Won Kim Sae Kyung Joo Sunyoung Park Jeong Hwan Park Yun Kyung Kang So-Young Jin Mee Soo Chang Expression patterns of STAT3, ERK and estrogen-receptor α are associated with development and histologic severity of hepatic steatosis: a retrospective study Diagnostic Pathology Hepatic steatosis Non-alcoholic Alcoholic mTOR pSTAT3 pERK |
| title | Expression patterns of STAT3, ERK and estrogen-receptor α are associated with development and histologic severity of hepatic steatosis: a retrospective study |
| title_full | Expression patterns of STAT3, ERK and estrogen-receptor α are associated with development and histologic severity of hepatic steatosis: a retrospective study |
| title_fullStr | Expression patterns of STAT3, ERK and estrogen-receptor α are associated with development and histologic severity of hepatic steatosis: a retrospective study |
| title_full_unstemmed | Expression patterns of STAT3, ERK and estrogen-receptor α are associated with development and histologic severity of hepatic steatosis: a retrospective study |
| title_short | Expression patterns of STAT3, ERK and estrogen-receptor α are associated with development and histologic severity of hepatic steatosis: a retrospective study |
| title_sort | expression patterns of stat3 erk and estrogen receptor α are associated with development and histologic severity of hepatic steatosis a retrospective study |
| topic | Hepatic steatosis Non-alcoholic Alcoholic mTOR pSTAT3 pERK |
| url | http://link.springer.com/article/10.1186/s13000-018-0698-8 |
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