PMID- 35853010 OWN - NLM STAT- MEDLINE DCOM- 20220812 LR - 20240216 IS - 1522-1547 (Electronic) IS - 0193-1857 (Print) IS - 0193-1857 (Linking) VI - 323 IP - 3 DP - 2022 Sep 1 TI - SLAMF1 is expressed and secreted by hepatocytes and the liver in nonalcoholic fatty liver disease. PG - G177-G187 LID - 10.1152/ajpgi.00289.2021 [doi] AB - Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent forms of chronic liver disease in the United States and worldwide. Nonalcoholic steatohepatitis (NASH), the most advanced form of NAFLD, is characterized by hepatic steatosis associated with inflammation and hepatocyte death. No treatments are currently available for NASH other than lifestyle changes, and the disease lacks specific biomarkers. The signaling lymphocytic activation molecule family 1 (SLAMF1) protein is a self-ligand receptor that plays a role in orchestrating an immune response to some pathogens and cancers. We found that livers from humans and mice with NASH showed a more prominent immunohistochemistry staining for SLAMF1 than non-NASH controls. Furthermore, SLAMF1 levels are significantly increased in NASH plasma samples from mice and humans compared with their respective controls. In mice, the levels of SLAMF1 correlated significantly with the severity of the NASH phenotype. To test whether SLAMF 1 is expressed by hepatocytes, HepG2 cells and primary murine hepatocytes were treated with palmitic acid (PA) to induce a state of lipotoxicity mimicking NASH. We found that PA treatments of HepG2 cells and primary hepatocytes lead to significant increases in SLAMF1 levels. The downregulation of SLAMF1 in HepG2 cells improved the cell viability and reduced cytotoxicity. The in vivo data using mouse and human NASH samples suggests a potential role for this protein as a noninvasive biomarker for NASH. The in vitro data suggest a role for SLAMF1 as a potential therapeutic target to prevent hepatocyte death in response to lipotoxicity.NEW & NOTEWORTHY This study identified for the first time SLAMF1 as a mediator of hepatocyte death in nonalcoholic fatty liver disease (NASH) and as a marker of NASH in humans. There are no pharmacological treatments available for NASH, and diagnostic tools are limited to invasive liver biopsies. Therefore, since SLAMF1 levels correlate with disease progression and SLAMF1 mediates cytotoxic effects, this protein can be used as a therapeutic target and a clinical biomarker of NASH. FAU - Gomez-Torres, Oscar AU - Gomez-Torres O AUID- ORCID: 0000-0001-5492-3343 AD - Department of Molecular and Cellular Physiology, Center for Cardiovascular Diseases and Sciences, and Center for Redox Biology and Cardiovascular Disease, Louisiana State University Health Sciences Center, Shreveport, Louisiana. AD - Facultad de Ciencias Ambientales y Bioquimica, Universidad de Castilla-La Mancha, Toledo, Spain. FAU - Amatya, Shripa AU - Amatya S AD - Department of Molecular and Cellular Physiology, Center for Cardiovascular Diseases and Sciences, and Center for Redox Biology and Cardiovascular Disease, Louisiana State University Health Sciences Center, Shreveport, Louisiana. FAU - Kamberov, Lilly AU - Kamberov L AD - Department of Molecular and Cellular Physiology, Center for Cardiovascular Diseases and Sciences, and Center for Redox Biology and Cardiovascular Disease, Louisiana State University Health Sciences Center, Shreveport, Louisiana. FAU - Dhaibar, Hemangini A AU - Dhaibar HA AD - Department of Molecular and Cellular Physiology, Center for Cardiovascular Diseases and Sciences, and Center for Redox Biology and Cardiovascular Disease, Louisiana State University Health Sciences Center, Shreveport, Louisiana. FAU - Khanna, Pranshu AU - Khanna P AD - Department of Molecular and Cellular Physiology, Center for Cardiovascular Diseases and Sciences, and Center for Redox Biology and Cardiovascular Disease, Louisiana State University Health Sciences Center, Shreveport, Louisiana. FAU - Rom, Oren AU - Rom O AD - Department of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana. FAU - Yurdagul, Arif Jr AU - Yurdagul A Jr AD - Department of Molecular and Cellular Physiology, Center for Cardiovascular Diseases and Sciences, and Center for Redox Biology and Cardiovascular Disease, Louisiana State University Health Sciences Center, Shreveport, Louisiana. FAU - Orr, A Wayne AU - Orr AW AD - Department of Molecular and Cellular Physiology, Center for Cardiovascular Diseases and Sciences, and Center for Redox Biology and Cardiovascular Disease, Louisiana State University Health Sciences Center, Shreveport, Louisiana. AD - Department of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana. FAU - Nunez, Kelly AU - Nunez K AD - Institute of Translational Research, Ochsner Health System, New Orleans, Louisiana. FAU - Thevenot, Paul AU - Thevenot P AD - Institute of Translational Research, Ochsner Health System, New Orleans, Louisiana. FAU - Cohen, Ari AU - Cohen A AD - Institute of Translational Research, Ochsner Health System, New Orleans, Louisiana. AD - Ochsner Transplant Institute, New Orleans, Louisiana. FAU - Samant, Hrishikesh AU - Samant H AD - Ochsner Transplant Institute, New Orleans, Louisiana. FAU - Alexander, Jonathan S AU - Alexander JS AD - Department of Molecular and Cellular Physiology, Center for Cardiovascular Diseases and Sciences, and Center for Redox Biology and Cardiovascular Disease, Louisiana State University Health Sciences Center, Shreveport, Louisiana. FAU - Burgos-Ramos, Emma AU - Burgos-Ramos E AD - Department of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana. FAU - Chapa-Rodriguez, Adrian AU - Chapa-Rodriguez A AD - Department of Pediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital, Little Rock, Arkansas. FAU - Cruz-Topete, Diana AU - Cruz-Topete D AUID- ORCID: 0000-0001-6315-6027 AD - Department of Molecular and Cellular Physiology, Center for Cardiovascular Diseases and Sciences, and Center for Redox Biology and Cardiovascular Disease, Louisiana State University Health Sciences Center, Shreveport, Louisiana. LA - eng GR - R00 HL150233/HL/NHLBI NIH HHS/United States GR - K99 HL150233/HL/NHLBI NIH HHS/United States GR - R01 DK134011/DK/NIDDK NIH HHS/United States GR - R00 HL145131/HL/NHLBI NIH HHS/United States GR - R01 HL141155/HL/NHLBI NIH HHS/United States GR - P20 GM121307/GM/NIGMS NIH HHS/United States GR - K01 HL144882/HL/NHLBI NIH HHS/United States GR - R01 HL098435/HL/NHLBI NIH HHS/United States GR - R01 HL133497/HL/NHLBI NIH HHS/United States PT - Journal Article DEP - 20220719 PL - United States TA - Am J Physiol Gastrointest Liver Physiol JT - American journal of physiology. Gastrointestinal and liver physiology JID - 100901227 RN - 0 (SLAMF1 protein, human) RN - 0 (Signaling Lymphocytic Activation Molecule Family) RN - 0 (Slamf1 protein, mouse) RN - 169535-43-7 (Signaling Lymphocytic Activation Molecule Family Member 1) SB - IM MH - Animals MH - Hepatocytes/metabolism MH - Humans MH - Liver/metabolism MH - Liver Cirrhosis/metabolism MH - Mice MH - *Non-alcoholic Fatty Liver Disease/metabolism MH - Signaling Lymphocytic Activation Molecule Family/metabolism MH - Signaling Lymphocytic Activation Molecule Family Member 1/metabolism PMC - PMC9377786 OTO - NOTNLM OT - SLAMF1 OT - biomarkers OT - nonalcoholic fatty liver disease COIS- No conflicts of interest, financial or otherwise, are declared by the authors. EDAT- 2022/07/20 06:00 MHDA- 2022/08/13 06:00 PMCR- 2023/09/01 CRDT- 2022/07/19 13:33 PHST- 2022/07/20 06:00 [pubmed] PHST- 2022/08/13 06:00 [medline] PHST- 2022/07/19 13:33 [entrez] PHST- 2023/09/01 00:00 [pmc-release] AID - GI-00289-2021 [pii] AID - 10.1152/ajpgi.00289.2021 [doi] PST - ppublish SO - Am J Physiol Gastrointest Liver Physiol. 2022 Sep 1;323(3):G177-G187. doi: 10.1152/ajpgi.00289.2021. Epub 2022 Jul 19.