Cellular and molecular basis of liver regeneration

Bangru, Sushant; Kalsotra, Auinash

doi:10.1016/j.semcdb.2019.12.004

Cited by 30 publications

(28 citation statements)

References 182 publications

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“…Hepatic epithelial injury triggers a strong regenerative response through a variety of mechanisms, including hepatocyte renewal, inflammation, and extracellular matrix remodeling. 74 , 75 An essential component of liver regeneration under physiologic and pathologic conditions is the remarkable plasticity of hepatocytes, which are able to dedifferentiate and become progenitor-like. 76 Furthermore, recent work has shown that the transforming growth factor β signaling pathway is critical for liver regeneration after partial hepatectomy, in part via activating hepatocyte EMT reprogramming in concert with the transcriptional co-activator YAP.…”

Section: Epithelial Splicing Regulatory Protein 2 Splicing Factor Regmentioning

confidence: 99%

Alternative Splicing in Hepatocellular Carcinoma

Lee

Alcedo

Kim

et al. 2020

Cellular and Molecular Gastroenterology and Hepatology

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Alternative splicing controls key metabolic pathways important for liver development and hepatocyte homeostasis. Global changes in RNA binding proteins yield novel tumor-associated transcripts and protein isoforms in hepatocellular carcinoma. Studies addressing these mechanisms illuminate new diagnostic, prognostic, and therapeutic targets for hepatocellular carcinoma. Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancer cases, with more than 850,000 new diagnoses per year globally. Recent trends in the United States have shown that liver cancer mortality has continued to increase in both men and women, while 5year survival remains below 20%. Understanding key mechanisms that drive chronic liver disease progression to HCC can reveal new therapeutic targets and biomarkers for early detection of HCC. In that regard, many studies have underscored the importance of alternative splicing as a source of novel HCC prognostic markers and disease targets. Alternative splicing of pre-mRNA provides functional diversity to the genome, and endows cells with the ability to rapidly remodel the proteome. Genes that control fundamental processes, such as metabolism, cell proliferation, and apoptosis, are altered globally in HCC by alternative splicing. This review highlights the major splicing factors, RNA binding proteins, transcriptional targets, and signaling pathways that are of key relevance to HCC. We highlight primary research from the past 3-5 years involving functional interrogation of alternative splicing in rodent and human liver, using both large-scale transcriptomic and focused mechanistic approaches. Because this is a rapidly advancing field, we anticipate that it will be transformative for the future of basic liver biology, as well as HCC diagnosis and management.

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Section: Epithelial Splicing Regulatory Protein 2 Splicing Factor Regmentioning

confidence: 99%

Alternative Splicing in Hepatocellular Carcinoma

Lee

Alcedo

Kim

et al. 2020

Cellular and Molecular Gastroenterology and Hepatology

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“…In the normal state, the liver is a quiescent tissue, and most mature hepatocytes are out of the replicating phase. However, the liver has the capacity to regenerate in response to cell loss, such as after hepatectomy or drug-induced hepatic injury [24,25]. In both hepatectomized and CCl4-treated livers, the expression of HDGF was increased in hepatocytes, and the induction of HDGF was observed before the DNA synthesis peaked.…”

Section: Involvement Of Hdgf In Non-transformed Hepatocyte Proliferationmentioning

confidence: 99%

Hepatoma-Derived Growth Factor: An Overview and Its Role as a Potential Therapeutic Target Molecule for Digestive Malignancies

Enomoto

Nakamura

Nishikawa

et al. 2020

IJMS

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Hepatoma-derived growth factor (HDGF) was identified in research seeking to find a novel growth factor for hepatoma cells. Subsequently, four HDGF-related proteins were identified, and these proteins are considered to be members of a new gene family. HDGF has a growth-stimulating role, an angiogenesis-inducing role, and a probable anti-apoptotic role. HDGF is ubiquitously expressed in non-cancerous tissues, and participates in organ development and in the healing of damaged tissues. In addition, the high expression of HDGF was reported to be closely associated with unfavorable clinical outcomes in several malignant diseases. Thus, HDGF is considered to contribute to the development and progression of malignant disease. We herein provide a brief overview of the factor and its functions in relation to benign and malignant cells. We also describe its possible role as a target molecule for digestive malignancies.

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“…For instance, mammals, who have suffered a pronounced phylogenetic decline in regenerative capacity, are capable of restoring neither amputated limbs nor other external appendages (the repair is limited to wound healing). At the same time, regeneration of certain organs and structures in mammals is morphologically consistent and results in complete functional recovery; characteristic examples include the restoration of the auricle tissue after a perforating wound (Williams-Boyce and Daniel, 1986) and restoration of the liver mass after massive resections (Bangru and Kalsotra, 2020).…”

Section: Resultsmentioning

confidence: 99%

Evolution of Regeneration in Animals: A Tangled Story

2021

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The evolution of regenerative capacity in multicellular animals represents one of the most complex and intriguing problems in biology. How could such a seemingly advantageous trait as self-repair become consistently attenuated by the evolution? This review article examines the concept of the origin and nature of regeneration, its connection with the processes of embryonic development and asexual reproduction, as well as with the mechanisms of tissue homeostasis. The article presents a variety of classical and modern hypotheses explaining different trends in the evolution of regenerative capacity which is not always beneficial for the individual and notably for the species. Mechanistically, these trends are driven by the evolution of signaling pathways and progressive restriction of differentiation plasticity with concomitant advances in adaptive immunity. Examples of phylogenetically enhanced regenerative capacity are considered as well, with appropriate evolutionary reasoning for the enhancement and discussion of its molecular mechanisms.

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Cellular and molecular basis of liver regeneration

Cited by 30 publications

References 182 publications

Alternative Splicing in Hepatocellular Carcinoma

Alternative Splicing in Hepatocellular Carcinoma

Hepatoma-Derived Growth Factor: An Overview and Its Role as a Potential Therapeutic Target Molecule for Digestive Malignancies

Evolution of Regeneration in Animals: A Tangled Story

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