Limits...
Hepatic SATB1 induces paracrine activation of hepatic stellate cells and is upregulated by HBx

View Article: PubMed Central - PubMed

ABSTRACT

Chronic hepatitis B virus (HBV) infection is a major cause of chronic liver diseases, but its involvement in hepatic fibrogenesis remains unclear. Special AT-rich binding protein 1 (SATB1) has been implicated in reprogramming chromatin organization and transcription profiles in many cancers and non-cancer-related conditions. We found that hepatic SATB1 expression was significantly up-regulated in fibrotic tissues from chronic hepatitis B virus (HBV)-infected patients and HBV transgenic (HBV-Tg) mouse model. Knockdown of SATB1 in the liver significantly alleviated CCl4-induced fibrosis in HBV-Tg mouse model. Moreover, we suggested HBV encoded x protein (HBx) induced SATB1 expression through activation of JNK and ERK pathways. Enforced expression of SATB1 in hepatocytes promoted the activation and proliferation of hepatic stellate cells (HSCs) by secretion of connective tissue growth factor (CTGF), Interleukin-6 (IL-6) and platelet derived growth factor-A (PDGF-AA). Our findings demonstrated that HBx upregulated hepatic SATB1 which exerted pro-fibrotic effects by paracrine activation of stellate cells in HBV-related fibrosis.

No MeSH data available.


Related in: MedlinePlus

SATB1 participates in HBX-mediated fibrogenesis by modulation of IL-6, PDGF-AA and CTGF expression.(a) The mRNA levels of SATB1, IL-6, PDGF-AA and CTGF were analyzed by Real-time PCR in L02 and PHC cells transduced with lenti-SATB1 and lenti-ctrl virus. (n = 3). *P < 0.05, **P < 0.01 vs. L02-Vector or PHC-Vector. (b) Silencing SATB1 in L02-HBx cells for 48 h, mRNA extracts were used for analyzing SATB1, IL-6, PDGF-AA, and CTGF expression by Real-time PCR. (n = 3). *P < 0.05, **P < 0.01 vs. L02-HBx NC. (c,d) Silencing SATB1 expression in L02-HBx cells for 48 h, the conditioned medium were used to determine the secretion amount of IL-6 and CTGF. (n = 3). *P < 0.05, **P < 0.01 vs. L02-HBx NC or L02-Vector NC.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5121621&req=5

f7: SATB1 participates in HBX-mediated fibrogenesis by modulation of IL-6, PDGF-AA and CTGF expression.(a) The mRNA levels of SATB1, IL-6, PDGF-AA and CTGF were analyzed by Real-time PCR in L02 and PHC cells transduced with lenti-SATB1 and lenti-ctrl virus. (n = 3). *P < 0.05, **P < 0.01 vs. L02-Vector or PHC-Vector. (b) Silencing SATB1 in L02-HBx cells for 48 h, mRNA extracts were used for analyzing SATB1, IL-6, PDGF-AA, and CTGF expression by Real-time PCR. (n = 3). *P < 0.05, **P < 0.01 vs. L02-HBx NC. (c,d) Silencing SATB1 expression in L02-HBx cells for 48 h, the conditioned medium were used to determine the secretion amount of IL-6 and CTGF. (n = 3). *P < 0.05, **P < 0.01 vs. L02-HBx NC or L02-Vector NC.

Mentions: We have showed that SATB1, as the downstream of HBx, responsible for the paracrine activation of LX-2 by secretion of IL-6, PDGF-AA and CTGF (Fig. 7a). Next, we analyzed the role of SATB1 in HBx-mediated activation of HSCs. Silencing SATB1 in HBx-transfected cells could down-regulated the mRNA levels of PDGF-AA and CTGF (Fig. 7b). Besides, knockdown of SATB1 decreased the secretion of IL-6 and CTGF in HBx-transfected L02 cells (Fig. 7c,d). All together, these results suggest that SATB1 involves in HBx-mediated HSCs activation by regulation of cytokines IL-6, PDGF-AA and CTGF.


Hepatic SATB1 induces paracrine activation of hepatic stellate cells and is upregulated by HBx
SATB1 participates in HBX-mediated fibrogenesis by modulation of IL-6, PDGF-AA and CTGF expression.(a) The mRNA levels of SATB1, IL-6, PDGF-AA and CTGF were analyzed by Real-time PCR in L02 and PHC cells transduced with lenti-SATB1 and lenti-ctrl virus. (n = 3). *P < 0.05, **P < 0.01 vs. L02-Vector or PHC-Vector. (b) Silencing SATB1 in L02-HBx cells for 48 h, mRNA extracts were used for analyzing SATB1, IL-6, PDGF-AA, and CTGF expression by Real-time PCR. (n = 3). *P < 0.05, **P < 0.01 vs. L02-HBx NC. (c,d) Silencing SATB1 expression in L02-HBx cells for 48 h, the conditioned medium were used to determine the secretion amount of IL-6 and CTGF. (n = 3). *P < 0.05, **P < 0.01 vs. L02-HBx NC or L02-Vector NC.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5121621&req=5

f7: SATB1 participates in HBX-mediated fibrogenesis by modulation of IL-6, PDGF-AA and CTGF expression.(a) The mRNA levels of SATB1, IL-6, PDGF-AA and CTGF were analyzed by Real-time PCR in L02 and PHC cells transduced with lenti-SATB1 and lenti-ctrl virus. (n = 3). *P < 0.05, **P < 0.01 vs. L02-Vector or PHC-Vector. (b) Silencing SATB1 in L02-HBx cells for 48 h, mRNA extracts were used for analyzing SATB1, IL-6, PDGF-AA, and CTGF expression by Real-time PCR. (n = 3). *P < 0.05, **P < 0.01 vs. L02-HBx NC. (c,d) Silencing SATB1 expression in L02-HBx cells for 48 h, the conditioned medium were used to determine the secretion amount of IL-6 and CTGF. (n = 3). *P < 0.05, **P < 0.01 vs. L02-HBx NC or L02-Vector NC.
Mentions: We have showed that SATB1, as the downstream of HBx, responsible for the paracrine activation of LX-2 by secretion of IL-6, PDGF-AA and CTGF (Fig. 7a). Next, we analyzed the role of SATB1 in HBx-mediated activation of HSCs. Silencing SATB1 in HBx-transfected cells could down-regulated the mRNA levels of PDGF-AA and CTGF (Fig. 7b). Besides, knockdown of SATB1 decreased the secretion of IL-6 and CTGF in HBx-transfected L02 cells (Fig. 7c,d). All together, these results suggest that SATB1 involves in HBx-mediated HSCs activation by regulation of cytokines IL-6, PDGF-AA and CTGF.

View Article: PubMed Central - PubMed

ABSTRACT

Chronic hepatitis B virus (HBV) infection is a major cause of chronic liver diseases, but its involvement in hepatic fibrogenesis remains unclear. Special AT-rich binding protein 1 (SATB1) has been implicated in reprogramming chromatin organization and transcription profiles in many cancers and non-cancer-related conditions. We found that hepatic SATB1 expression was significantly up-regulated in fibrotic tissues from chronic hepatitis B virus (HBV)-infected patients and HBV transgenic (HBV-Tg) mouse model. Knockdown of SATB1 in the liver significantly alleviated CCl4-induced fibrosis in HBV-Tg mouse model. Moreover, we suggested HBV encoded x protein (HBx) induced SATB1 expression through activation of JNK and ERK pathways. Enforced expression of SATB1 in hepatocytes promoted the activation and proliferation of hepatic stellate cells (HSCs) by secretion of connective tissue growth factor (CTGF), Interleukin-6 (IL-6) and platelet derived growth factor-A (PDGF-AA). Our findings demonstrated that HBx upregulated hepatic SATB1 which exerted pro-fibrotic effects by paracrine activation of stellate cells in HBV-related fibrosis.

No MeSH data available.


Related in: MedlinePlus