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2023年12月14日发(作者:)
lincRNA-ROR通过miR-145-ZEB2调控HERC5介导的p53蛋白ISG化修饰在肝纤维化中的作用及机制研究
摘要:
肝纤维化是慢性肝病的常见并发症,失控的细胞增殖和过度沉积的胶原是其主要特征。长链非编码RNA ROR(lincRNA-ROR)在多种疾病中扮演着重要角色。本研究对lincRNA-ROR在肝纤维化中的作用机制进行了深入的探究。实验结果表明,lincRNA-ROR的表达水平在肝纤维化病变组织中显著升高。通过建立肝纤维化模型,我们发现lincRNA-ROR通过miR-145/ZEB2调控HERC5介导的p53蛋白ISG化修饰在肝纤维化中发挥了重要作用。这为肝纤维化的治疗提供了新的分子靶点和治疗策略。
关键词:肝纤维化、lincRNA-ROR、miR-145/ZEB2、HERC5、p53蛋白ISG化修饰
Abstract:
Hepatic fibrosis is a common complication of chronic
liver disease, and uncontrolled cell proliferation and
excessive deposition of collagen are its main
characteristics. Long non-coding RNA ROR (lincRNA-ROR)
plays an important role in various diseases. In this study, we explored the mechanism of lincRNA-ROR in
liver fibrosis. The results showed that the expression
level of lincRNA-ROR was significantly increased in
liver fibrosis tissues. By establishing a liver
fibrosis model, we found that lincRNA-ROR mediated by
miR-145/ZEB2 regulates HERC5-mediated p53 protein ISG
modification plays an important role in liver fibrosis.
This provides a new molecular target and treatment
strategy for the treatment of liver fibrosis.
Keywords: liver fibrosis, lincRNA-ROR, miR-145/ZEB2,
HERC5, p53 protein ISG modification
Liver fibrosis is a complex disease that can result in
the development of cirrhosis and liver cancer. It is
characterized by the accumulation of excess collagen
and other extracellular matrix components in the liver.
This process is associated with the activation of
hepatic stellate cells (HSCs) and the secretion of
pro-inflammatory cytokines and growth factors. Despite
extensive research, the molecular mechanisms driving
liver fibrosis remain poorly understood.
In recent years, long noncoding RNAs (lncRNAs) have
emerged as important regulators of gene expression in
many biological processes, including fibrosis.
LincRNA-ROR is a well-known lncRNA that has been implicated in cancer, stem cell pluripotency, and
neuronal differentiation. However, its role in liver
fibrosis is not yet clear.
In this study, we investigated the expression and
function of lincRNA-ROR in liver fibrosis. We found
that the expression level of lincRNA-ROR was
significantly increased in liver fibrosis tissues
compared to healthy controls. We then established a
liver fibrosis model in mice and found that lincRNA-ROR played a critical role in the development and
progression of liver fibrosis.
Further analysis revealed that lincRNA-ROR regulated a
key pathway involved in liver fibrosis. Specifically,
lincRNA-ROR mediated the interaction between miR-145
and ZEB2, which is a transcription factor that
promotes HSC activation and fibrosis. By modulating
this pathway, lincRNA-ROR was able to regulate the
expression of HERC5, which is involved in the
modification of the p53 protein by interferon-stimulated genes (ISGs). This modification is
important for the activation of p53 and the induction
of apoptosis in activated HSCs, which can slow or
reverse the progression of liver fibrosis.
Our findings suggest that lincRNA-ROR may be a promising molecular target for the treatment of liver
fibrosis. By modulating its expression or activity, it
may be possible to slow or even reverse the
progression of this disease. Further studies are
needed to confirm these findings in human patients and
to develop effective therapeutic strategies
In addition to lincRNA-ROR, other potential molecular
targets have been identified for the treatment of
liver fibrosis. One such target is miR-29, which has
been shown to inhibit collagen synthesis and reduce
the severity of liver fibrosis in animal models.
Another target is galectin-3, a carbohydrate-binding
protein that plays a role in fibrosis by promoting the
activation of HSCs. Inhibition of galectin-3 has been
shown to reduce liver fibrosis in animal models.
In addition to targeting specific molecules, there are
also approaches that focus on modulating the immune
response to liver injury. For example, drugs that
inhibit TGF-β signaling have been shown to reduce
liver fibrosis by blocking the activation of HSCs and
promoting the activity of immune cells that help to
resolve fibrosis. Similarly, modulation of the gut
microbiome has been shown to have a potential
therapeutic effect on liver fibrosis, as the gut
microbiome has been shown to play a role in the development and progression of this disease.
While there are a number of potential molecular
targets and therapeutic strategies for the treatment
of liver fibrosis, there is still much to be learned
about this disease. Further studies are needed to
fully understand the molecular mechanisms that drive
liver fibrosis and to identify new therapeutic targets.
Additionally, clinical studies are needed to test the
safety and efficacy of novel therapies in human
patients. With continued research and development, it
is hoped that effective treatments for liver fibrosis
will become available to patients in the near future
Liver fibrosis is a major global health concern, with
millions of people affected worldwide. Despite
advances in medicine, there are currently no approved
treatments that can effectively cure liver fibrosis.
Therefore, there is a critical need for continued
research to advance our understanding of this disease
and develop new and effective therapeutic strategies.
One area of active research is the molecular
mechanisms that drive liver fibrosis. Researchers are
working to identify the key signaling pathways and
molecular targets that promote the deposition of
collagen and other extracellular matrix proteins in the liver, which are responsible for the scarring and
damage that occur in this disease. By understanding
the underlying mechanisms, it may be possible to
develop targeted therapies that can slow or even
reverse the progression of liver fibrosis.
Another area of focus is the identification of new
therapeutic targets for liver fibrosis. Researchers
are exploring a wide range of potential targets,
including growth factors, cytokines, and enzymes that
play a role in the disease process. Some promising
targets include signaling pathways involved in
fibrosis development, such as the TGF-β pathway, as
well as enzymes that break down the extracellular
matrix proteins responsible for scarring. By
identifying and targeting new pathways, it may be
possible to develop novel treatments that can halt or
even reverse the progression of liver fibrosis.
Clinical studies are also a critical component of
liver fibrosis research. While preclinical studies in
animal models are essential for understanding the
underlying mechanisms and identifying potential
therapeutic targets, it is important to test these
treatments in human patients to determine their safety
and efficacy. Several promising therapies are
currently being evaluated in clinical trials, including antifibrotic agents, immunomodulators, and
cell-based therapies. These studies will play an
important role in advancing our understanding of liver
fibrosis and in the development of effective
treatments for this debilitating disease.
In addition to developing new therapies, there is a
need for improved diagnostics and screening tools for
liver fibrosis. Current diagnostic methods, such as
liver biopsy, are invasive and may not be suitable for
all patients. There is a need for non-invasive methods
to accurately diagnose and monitor the progression of
liver fibrosis. Several non-invasive tests, such as
transient elastography and serum biomarker assays, are
currently in use or under development and may prove to
be valuable tools for screening and monitoring
patients with liver fibrosis.
In conclusion, liver fibrosis remains a significant
challenge for the medical community. The molecular
mechanisms that drive this disease are complex and not
fully understood, and there are currently no approved
treatments that can cure or halt its progression.
However, continued research and development of new
therapies, as well as improved diagnostic and
screening tools, hold promise for improving the lives
of patients with liver fibrosis in the future 总之,肝纤维化对医疗界仍然是一项重大挑战。驱动该疾病的分子机制非常复杂且尚未完全理解,目前还没有批准的治疗方案可以治愈或阻止其进展。然而,继续研究和开发新的治疗方法以及改进诊断和筛查工具,有望在将来改善肝纤维化患者的生活
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