Citations 2
Knockout of sulfatase 2 is associated with decreased steatohepatitis and fibrosis in a mouse model of nonalcoholic fatty liver disease
Kim, Tae Hyo , Banini, Bubu A. , Asumda, Faizal Z., Campbell, Nellie A. , Hu, Chunling , Moser, Catherine D., Shire, Abdirashid M., Han, Shaoshan , Ma, Chenchao , Krishnan, Anuradha, Mounajjed, Taofic, White, Thomas A. , Roberts, Lewis R. , Charlton, Michael R, Roberts, Lewis R , Hu, Chunling , Campbell, Nellie A , Gores, Gregory J. , LeBrasseur, Nathan K. , Charlton, Michael
American Journal of Physiology-Gastrointestinal and Liver Physiology | July 20, 2020 | Volume: 319 | Issue: 3 | Pages: G333-G344
We report for the first time that in wild-type (WT) mice, fast-food diet (FFD) induced a threefold increase in hepatic Sulf2 mRNA and a 2.2-fold increase in sulfatase 2 (SULF2) protein expression compared with WT mice on standard chow diet (SC). We showed that knockout of SULF2 ameliorates FFD-induced obesity, hyperlipidemia, steatohepatitis, and fibrosis. These data, along with work from other laboratories, suggest that SULF2 may be critical to the ability of the liver to progress to nonalcoholic steatohepatitis and fibrosis in conditions of overnutrition.
Transcriptional Induction of Periostin by a Sulfatase 2–TGFβ1–SMAD Signaling Axis Mediates Tumor Angiogenesis in Hepatocellular Carcinoma
Chen, Gang , Nakamura, Ikuo , Dhanasekaran, Renumathy , Iguchi, Eriko , Tolosa, Ezequiel J. , Romecín, Paola , Vera, Renzo E., Almada, Luciana L. , Miamen, Alexander G., Chaiteerakij, Roongruedee , Zhou, Mengtao , Moser, Catherine D., Han, Shaoshan , Hu, Chunling , Banini, Bubu A. , Oseini, Abdul M., Fang, Yong , Yang, Dongye , Shaleh, Hassan M., Wang, Shaoqing , Wu, Dehai, Song, Tao , Lee, Ju‐Seog , Thorgeirsson, Snorri S., Chevet, Éric , Shah, Vijay H. , Fernández-Zapico, Martín E. , Roberts, Lewis R. , Romecin, Paola A, Asiedu, Michael K. , Chen, Yichun, Nakamura, Ikuo, Chaiteerakij, Roongruedee , Chen, Yi‐Chun , Roberts, Lewis R , Dhanasekaran, Renumathy , Hu, Chunling , Chen, Gang , Chevet, Eric
Cancer Research | November 21, 2016 | Volume: 77 | Issue: 3 | Pages: 632-645
Abstract Existing antiangiogenic approaches to treat metastatic hepatocellular carcinoma (HCC) are weakly effectual, prompting further study of tumor angiogenesis in this disease setting. Here, we report a novel role for sulfatase 2 (SULF2) in driving HCC angiogenesis. Sulf2-deficient mice (Sulf2 KO) exhibited resistance to diethylnitrosamine-induced HCC and did not develop metastases like wild-type mice (Sulf2 WT). The smaller and less numerous tumors formed in Sulf2 KO mice exhibited a markedly lower microvascular density. In human HCC cells, SULF2 overexpression increased endothelial proliferation, adhesion, chemotaxis, and tube formation in a paracrine fashion. Mechanistic analyses identified the extracellular matrix protein periostin (POSTN), a ligand of αvβ3/5 integrins, as an effector protein in SULF2-induced angiogenesis. POSTN silencing in HCC cells attenuated SULF2-induced angiogenesis and tumor growth in vivo. The TGFβ1/SMAD pathway was identified as a critical signaling axis between SULF2 and upregulation of POSTN transcription. In clinical HCC specimens, elevated levels of SULF2 correlated with increased microvascular density, POSTN levels, and relatively poorer patient survival. Together, our findings define an important axis controlling angiogenesis in HCC and a mechanistic foundation for rational drug development. Cancer Res; 77(3); 632–45. ©2016 AACR.