Journal: Molecular Medicine

Article Title: SARS-CoV-2 and interferon blockade

doi: 10.1186/s10020-020-00231-w

Figure Lengend Snippet: ACE2 is a key enzyme in the RAS, catalyzing the metabolism of Ang II to Ang(1-7) and Ang I to Ang(1-9). ACE2 also mediates degradation of ACE-catalyzed breakdown products, Des-arg9-Bk (B1R agonist) and Lys-des-arg9-Bk. The net result of ACE2 in these two systems is to counterbalance ACE/Ang II/AT1R and Bradykinin/Des-arg9-Bk/B1R pathways. Through its cellular binding and entry mechanisms, SARS-CoV-2 is proposed to result in a reduction of ACE2, leading to elevations in Ang I and II, and leading to AT1R stimulation, and Des-arg9-Bk leading to B1R stimulation thus exacerbating inflammation, vascular leakage, and pro-fibrotic events. Potential therapeutics include those targeted to angiotensin and bradykinin system related peptides, in addition to peptides targeting the ACE2-viral spike (S) protein interaction

Article Snippet: Potential therapeutics include those targeted to angiotensin and bradykinin system related peptides, in addition to peptides targeting the ACE2-viral spike (S) protein interaction Several candidate therapeutics focus on the virus, targeting viral replication (remdesivir), viral entry (Arbidol, APN01, convalescent plasma, monoclonal antibodies (REGN-COV2), camostat mesylate), or critical viral proteins (protease inhibitors).

Techniques: Binding Assay

Journal: Signal Transduction and Targeted Therapy

Article Title: Angiotensin type 2 receptor activation promotes browning of white adipose tissue and brown adipogenesis

doi: 10.1038/sigtrans.2017.22

Figure Lengend Snippet: AT2R activation increases UCP1 and CITED1 expressions in white adipocytes. ( a and b ) Mouse white adipose cells (day 4) were transfected with control siRNAs, ACE2-siRNA, AT1R-siRNA or AT2R-siRNAs for 2–3 days, before treated without (−) (control) or with (+) AngII, ZD7155 or PD123319 for another 4 days. ( c ) Mouse white adipocytes were treated without (−) (control) or with (+) 100 nM M024/C21, 100 nM CGP42112 or PD123319 for 4 days. The representative immunoblots of protein expressions (UCP1, CITED1, ACE2, AT1R, AT2R, PPARγ, PRDM16, aP2 and actin), and the statistics (mean±s.e.m., n =4; normalized to actin densities) are shown accordingly. * P <0.05, ** P <0.01, *** P <0.001 versus control; # P <0.05 and ## P <0.01 between indicated pairs.

Article Snippet: For gene silencing of ACE2 ( ACE2 ), AT1R ( AGTR1 ) or AT2R ( AGTR2 ), adipose cells (day 4 after induction of differentiation) were transfected with a mouse ACE2 siRNA (sc-41401), AT1R siRNA (sc-29751), AT2R siRNA (sc-29753) or control siRNA (sc-37007) (Santa Cruz Biotechnology) as previously described., Specifically, adipose cells were incubated with Opti-MEM containing a complex of Lipofectamine-RNAiMAX transfection reagent (0.5% (v/v), Life Technologies, ThermoFisher Scientific) with siRNAs (25 n m ) for 4 h, followed by the addition of grown medium and incubated for another 2–3 days.

Techniques: Activation Assay, Transfection, Control, Western Blot

Journal: Signal Transduction and Targeted Therapy

Article Title: Angiotensin type 2 receptor activation promotes browning of white adipose tissue and brown adipogenesis

doi: 10.1038/sigtrans.2017.22

Figure Lengend Snippet: Signaling pathways underlying the AngII–AT2R-induced browning of white adipocytes. ( a – c ) Time course of the phosphorylation and total protein levels of ERK1/2, Akt and AMPK in mouse white adipocytes, without (−) (control) or with (+) exposure to AngII and ZD7155. Top panels, representative immunoblots; bottom panels, statistics (mean±s.e.m., n =3) of the optical density ratio between pERK and ERK, pAkt and Akt, or pAMPK and AMPK. ( d and e ) Mouse white adipose cells (day 4) were transfected with control siRNA, ERK1/2-siRNAs, Akt-siRNA or AMPK-siRNAs for 2–3 days before treated without (−) (control) or with (+) AngII and ZD7155 for 4 days. The representative immunoblots and the statistics (mean±s.e.m., n =4; normalized to actin densities) are shown accordingly. * P <0.05, ** P <0.01, *** P <0.001 versus control; # P <0.05 and ## P <0.01 between indicated pairs.

Article Snippet: For gene silencing of ACE2 ( ACE2 ), AT1R ( AGTR1 ) or AT2R ( AGTR2 ), adipose cells (day 4 after induction of differentiation) were transfected with a mouse ACE2 siRNA (sc-41401), AT1R siRNA (sc-29751), AT2R siRNA (sc-29753) or control siRNA (sc-37007) (Santa Cruz Biotechnology) as previously described., Specifically, adipose cells were incubated with Opti-MEM containing a complex of Lipofectamine-RNAiMAX transfection reagent (0.5% (v/v), Life Technologies, ThermoFisher Scientific) with siRNAs (25 n m ) for 4 h, followed by the addition of grown medium and incubated for another 2–3 days.

Techniques: Protein-Protein interactions, Phospho-proteomics, Control, Western Blot, Transfection

Journal: Bioscience Reports

Article Title: Physiological cyclic stretch up-regulates angiotensin-converting enzyme 2 expression to reduce proliferation and migration of vascular smooth muscle cells

doi: 10.1042/bsr20192012

Figure Lengend Snippet: Figure 1. Physiological stretch regulates ACE2 expression and activity, as well as other components of RAS in HASMCs

Article Snippet: EDTA (1 mM) and recombinant human ACE2 (25 ng, R&D Systems, U.S.A.) were used as a positive control.

Techniques: Expressing, Activity Assay

Journal: Bioscience Reports

Article Title: Physiological cyclic stretch up-regulates angiotensin-converting enzyme 2 expression to reduce proliferation and migration of vascular smooth muscle cells

doi: 10.1042/bsr20192012

Figure Lengend Snippet: Figure 2. ACE2 is involved in regulating proliferation and migration of HASMCs mediated by stretch Cultured HASMCs with different conditions were exposed to 10% stretch for 12 h; cells kept under static conditions were considered

Article Snippet: EDTA (1 mM) and recombinant human ACE2 (25 ng, R&D Systems, U.S.A.) were used as a positive control.

Techniques: Migration, Cell Culture

Journal: Bioscience Reports

Article Title: Physiological cyclic stretch up-regulates angiotensin-converting enzyme 2 expression to reduce proliferation and migration of vascular smooth muscle cells

doi: 10.1042/bsr20192012

Figure Lengend Snippet: Figure 3. The effect of stretch on ACE2 promoter activity and mRNA stability (A) Cultured HASMCs were co-transfected with pGL3-ACE2 promotor-luci and phRL-TK vectors for 24 h, then exposed to 10%

Article Snippet: EDTA (1 mM) and recombinant human ACE2 (25 ng, R&D Systems, U.S.A.) were used as a positive control.

Techniques: Activity Assay, Cell Culture, Transfection

Journal: Bioscience Reports

Article Title: Physiological cyclic stretch up-regulates angiotensin-converting enzyme 2 expression to reduce proliferation and migration of vascular smooth muscle cells

doi: 10.1042/bsr20192012

Figure Lengend Snippet: Figure 4. AP-1 and NF-κB were implicated in the regulation of ACE2 mediated by stretch (A) Potential binding sites of transcription factors in the promoter region of human ACE2 gene by TRANSFAC analysis (marked with gray boxes). (B) Cultured HASMCs were subject to 10% stretch for 0, 15, 30, 60, 120 min. Protein lysates were collected to detect

Article Snippet: EDTA (1 mM) and recombinant human ACE2 (25 ng, R&D Systems, U.S.A.) were used as a positive control.

Techniques: Binding Assay, Cell Culture

Journal: Bioscience Reports

Article Title: Physiological cyclic stretch up-regulates angiotensin-converting enzyme 2 expression to reduce proliferation and migration of vascular smooth muscle cells

doi: 10.1042/bsr20192012

Figure Lengend Snippet: Figure 5. PKCβII and JNK1/2 signaling pathways were involved in stretch-induced ACE2 expression (A) Effect of stretch on activations of mitogen-activated protein kinase (MAPK), Akt, and PKCβII pathways. Cultured HASMCs were

Article Snippet: EDTA (1 mM) and recombinant human ACE2 (25 ng, R&D Systems, U.S.A.) were used as a positive control.

Techniques: Protein-Protein interactions, Expressing, Cell Culture

Journal: Bioscience Reports

Article Title: Physiological cyclic stretch up-regulates angiotensin-converting enzyme 2 expression to reduce proliferation and migration of vascular smooth muscle cells

doi: 10.1042/bsr20192012

Figure Lengend Snippet: Figure 6. Scheme of the roles of ACE2 in physiological stretch mediated cellular functions of HASMCs and the underlying

Article Snippet: EDTA (1 mM) and recombinant human ACE2 (25 ng, R&D Systems, U.S.A.) were used as a positive control.

Techniques: