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[Mechanism of Ezhu-containing serum in inhibiting expression of Shh and Gli1 in hepatic stellate cells].
To explore the mechanism of Ezhu-containing serum in inhibiting the expression of sonic hedgehog(Shh) and glioma-associated oncogene homolog-1(Gli1) in hepatic stellate cells(HSCs) induced by leptin. Twenty sprague-dawley (SD) rats were randomly divided into 2 groups (n=10), and given Ezhu-decoction and physiological saline by gavage for 10 days to prepare drug-containing serums. The HSCs during the exponential growth phase were divided into 7 groups: blank control group, model group, hedgehog pathway inhibitor(cyclopamine) group, Ezhu group, Ezhu and cyclopamine group, hedgehog pathway agonost(pumorphamine) group, Ezhu and purmorphamine group. HSCs were cultured in vitro and induced with 100 μg•L ⁻¹ leptin(except for the blank control group), then treated separately with the corresponding drugs for 24 hours. After the cells were collected, HSCs proliferation was detected using MTT colorimetric assay; the expressions of Shh and Gli1 were determined by PT-PCR, Western blot and immunofluorescence, respectively. The expressions of Shh and Gli1 were significantly increased after the HSCs of rats were induced by leptin (compared with the blank control group, P<0.01). After being interfered with Hh pathway inhibitor (cyclopamine) and Ezhu-containing serum, the expressions of Shh and Gli1 were decreased significantly(compared with the model group, P<0.01). After Ezhu-containing serum was used to interfere the Hh pathway inhibitor group, the mRNA and protein expressions of Shh and Gli1 were decreased significantly(compared with the model group, P<0.01). After Ezhu-containing serum was used to interfere the purmorphamine group, the mRNA and protein expressions of Shh and Gli1 decreased significantly(compared with the purmorphamine group, P<0.01). Ezhu-containing serum plays an important role in inhibiting HSCs activation by taking part in hedgehog signaling pathway, so as to regulate the expression of Shh and Gli1 in leptin-induced HSCs and then inhibit liver fibrosis.
Authors : Feng Li-Li , Cao Wen-Fu ,
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Pathways :
WP1022: Hedgehog Signaling Pathway
WP1141: Hedgehog Signaling Pathway
WP116: Hedgehog Signaling Pathway
WP1263: Mitochondrial Gene Expression
WP1301: Mitochondrial Gene Expression
WP1353: Hedgehog Signaling Pathway
WP1368: Mitochondrial Gene Expression
WP1498: Dopminergic Neurogenesis
WP1603: Nicotine Activity on Chromaffin Cells
WP1821: Gene Expression
WP1872: Neurotransmitter uptake and Metabolism In Glial Cells
WP1963: The effect of Glucocorticoids on target gene expression
WP2231: Degradation of apoptotic cells
WP391: Mitochondrial Gene Expression
WP492: Hedgehog Signaling Pathway
WP574: Hedgehog Signaling Pathway
WP790: Hedgehog Signaling Pathway
WP905: Hedgehog Signaling Pathway
WP928: Mitochondrial Gene Expression
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[APEX1 APE APE1 APEX APX HAP1 REF1] DNA-(apurinic or apyrimidinic site) lyase (EC 3.1.-.-) (EC 4.2.99.18) (APEX nuclease) (APEN) (Apurinic-apyrimidinic endonuclease 1) (AP endonuclease 1) (APE-1) (REF-1) (Redox factor-1) [Cleaved into: DNA-(apurinic or apyrimidinic site) lyase, mitochondrial]
[KMT2A ALL1 CXXC7 HRX HTRX MLL MLL1 TRX1] Histone-lysine N-methyltransferase 2A (Lysine N-methyltransferase 2A) (EC 2.1.1.43) (ALL-1) (CXXC-type zinc finger protein 7) (Myeloid/lymphoid or mixed-lineage leukemia) (Myeloid/lymphoid or mixed-lineage leukemia protein 1) (Trithorax-like protein) (Zinc finger protein HRX) [Cleaved into: MLL cleavage product N320 (N-terminal cleavage product of 320 kDa) (p320); MLL cleavage product C180 (C-terminal cleavage product of 180 kDa) (p180)]
[rlmN OR1_00217] Dual-specificity RNA methyltransferase RlmN (EC 2.1.1.192) (23S rRNA (adenine(2503)-C(2))-methyltransferase) (23S rRNA m2A2503 methyltransferase) (Ribosomal RNA large subunit methyltransferase N) (tRNA (adenine(37)-C(2))-methyltransferase) (tRNA m2A37 methyltransferase)
[oli atp-9 atp9 prl-1 B13D24.340 NCU02250] ATP synthase subunit 9, mitochondrial (Lipid-binding protein)
[hprK OR1_01062] HPr kinase/phosphorylase (HPrK/P) (EC 2.7.11.-) (EC 2.7.4.-) (HPr(Ser) kinase/phosphorylase)
[rlmN OR221_0541] Probable dual-specificity RNA methyltransferase RlmN (EC 2.1.1.192) (23S rRNA (adenine(2503)-C(2))-methyltransferase) (23S rRNA m2A2503 methyltransferase) (Ribosomal RNA large subunit methyltransferase N) (tRNA (adenine(37)-C(2))-methyltransferase) (tRNA m2A37 methyltransferase)
[rlmN OR214_00171] Dual-specificity RNA methyltransferase RlmN (EC 2.1.1.192) (23S rRNA (adenine(2503)-C(2))-methyltransferase) (23S rRNA m2A2503 methyltransferase) (Ribosomal RNA large subunit methyltransferase N) (tRNA (adenine(37)-C(2))-methyltransferase) (tRNA m2A37 methyltransferase)
[rlmN OR16_10354] Dual-specificity RNA methyltransferase RlmN (EC 2.1.1.192) (23S rRNA (adenine(2503)-C(2))-methyltransferase) (23S rRNA m2A2503 methyltransferase) (Ribosomal RNA large subunit methyltransferase N) (tRNA (adenine(37)-C(2))-methyltransferase) (tRNA m2A37 methyltransferase)
[rlmN OR37_00801] Dual-specificity RNA methyltransferase RlmN (EC 2.1.1.192) (23S rRNA (adenine(2503)-C(2))-methyltransferase) (23S rRNA m2A2503 methyltransferase) (Ribosomal RNA large subunit methyltransferase N) (tRNA (adenine(37)-C(2))-methyltransferase) (tRNA m2A37 methyltransferase)
[hprK OR214_03799] HPr kinase/phosphorylase (HPrK/P) (EC 2.7.11.-) (EC 2.7.4.-) (HPr(Ser) kinase/phosphorylase)
[hprK OR16_19870] HPr kinase/phosphorylase (HPrK/P) (EC 2.7.11.-) (EC 2.7.4.-) (HPr(Ser) kinase/phosphorylase)
[lpxC asmB envA b0096 JW0094] UDP-3-O-acyl-N-acetylglucosamine deacetylase (UDP-3-O-acyl-GlcNAc deacetylase) (EC 3.5.1.108) (Protein EnvA) (UDP-3-O-[R-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase)
[ncd-2 G17A4.200 NCU03949] Nitronate monooxygenase (EC 1.13.12.16) (2-nitropropane dioxygenase) (2-NPD) (Nitroalkane oxidase)
[glyA OR1_02280] Serine hydroxymethyltransferase (SHMT) (Serine methylase) (EC 2.1.2.1)
[glyA OR16_35110] Serine hydroxymethyltransferase (SHMT) (Serine methylase) (EC 2.1.2.1)
[glyA OR221_0617] Serine hydroxymethyltransferase (SHMT) (Serine methylase) (EC 2.1.2.1)
[glyA OR37_03805] Serine hydroxymethyltransferase (SHMT) (Serine methylase) (EC 2.1.2.1)
[glyA OR214_01806] Serine hydroxymethyltransferase (SHMT) (Serine methylase) (EC 2.1.2.1)
[atp-2 B8B20.320 NCU05430] ATP synthase subunit beta, mitochondrial (EC 3.6.3.14)
[tgt OR1_00324] Queuine tRNA-ribosyltransferase (EC 2.4.2.29) (Guanine insertion enzyme) (tRNA-guanine transglycosylase)
[tgt OR1_03241] Queuine tRNA-ribosyltransferase (EC 2.4.2.29) (Guanine insertion enzyme) (tRNA-guanine transglycosylase)
[atpE OR1_03532] ATP synthase subunit c (ATP synthase F(0) sector subunit c) (F-type ATPase subunit c) (F-ATPase subunit c) (Lipid-binding protein)
[panC OR1_02334] Pantothenate synthetase (PS) (EC 6.3.2.1) (Pantoate--beta-alanine ligase) (Pantoate-activating enzyme)
[atp-6 oli2 NCM020 NCU16025] ATP synthase subunit a (F-ATPase protein 6)
[tdh OR16_22838] L-threonine 3-dehydrogenase (TDH) (EC 1.1.1.103)
[ndk OR1_00218] Nucleoside diphosphate kinase (NDK) (NDP kinase) (EC 2.7.4.6) (Nucleoside-2-P kinase)
[tgt OR37_02685] Queuine tRNA-ribosyltransferase (EC 2.4.2.29) (Guanine insertion enzyme) (tRNA-guanine transglycosylase)
[tgt OR214_03532] Queuine tRNA-ribosyltransferase (EC 2.4.2.29) (Guanine insertion enzyme) (tRNA-guanine transglycosylase)
[aceK OR214_03939] Isocitrate dehydrogenase kinase/phosphatase (IDH kinase/phosphatase) (IDHK/P) (EC 2.7.11.5) (EC 3.1.3.-)
[atpE OR214_01367] ATP synthase subunit c (ATP synthase F(0) sector subunit c) (F-type ATPase subunit c) (F-ATPase subunit c) (Lipid-binding protein)
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