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Review Open Access

PARP‑1 in liver diseases: Molecular mechanisms, therapeutic potential and emerging clinical applications (Review)

  • Authors:
    • Kaipeng Hu
    • Heng Tian
    • Shuxing Chen
    • Yuhan Liu
    • Ran Wei
    • Bangjie Chen
    • Yiwen Jia
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230071, P.R. China, Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, First Clinical Medical College, Anhui Medical University, Hefei, Anhui 230032, P.R. China
    Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 324
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    Published online on: September 22, 2025
       https://doi.org/10.3892/mmr.2025.13689
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Abstract

The liver, despite its capacity for self‑repair, faces major challenges when excessive damage leads to fibrosis and impaired function, potentially progressing to severe liver diseases, including cirrhosis, hepatocellular carcinoma (HCC) and non‑alcoholic fatty liver disease (NAFLD). Although advancements in understanding the molecular landscapes of these conditions have been made, clinical outcomes remain suboptimal. Therefore, novel therapeutic targets are necessary. Poly(ADP‑ribose) polymerase‑1 (PARP‑1), a pivotal enzyme in DNA damage response and repair, has emerged as a critical contributor to liver pathophysiology. The present review explores the expression, regulation and mechanism of action of PARP‑1 in various liver diseases, including viral hepatitis, alcoholic liver disease, NAFLD, hepatic fibrosis, HCC, drug‑induced liver injury and autoimmune liver diseases. The involvement of PARP‑1 in key cellular signaling pathways, particularly those associated with inflammation, apoptosis and immune regulation, highlights its clinical relevance as a biomarker and therapeutic target. The potential of PARP inhibitors to improve outcomes in patients with liver disease is discussed, both as stand‑alone treatments and in combination with modalities such as immune checkpoint inhibitors and DNA damage repair inhibitors. Leveraging recent advancements in PARP imaging and rare genetic biomarker research, this review underscores the potential of PARP‑1‑based diagnostics and therapies while advocating for future studies to overcome resistance mechanisms and expand therapeutic applications.
View Figures

Figure 1

lncRNA-HUR1 suppresses the intrinsic
apoptosis pathway by inhibiting PARP-1 cleavage, leading to HCC
cell proliferation. HCC, hepatocellular carcinoma; lnc, long
non-coding; PARP-1, poly(ADP-ribose) polymerase-1.

Figure 2

Main molecular targets regulated by
PARP-1 in HF. PARP-1 detects damaged cellular DNA and initiates the
ASK1-JNK pathway, leading to EMT and increased collagen I/III and
α-SMA expression, which exacerbates HF. α-SMA, α-smooth muscle
actin; ASK1, apoptotic signal-regulating kinase 1; EMT,
epithelial-to-mesenchymal transition; HF, hepatic fibrosis; HSCs,
hepatic stellate cells; KCs, Kupffer cells; PARP-1,
poly(ADP-ribose) polymerase-1.

Figure 3

PARP-1 suppresses transcription by
preventing PPARα from recruiting the PPARα/SIRT1/PGC-1α complex to
target promoters. This may have specific implications in the
prevention and treatment of NAFLD when PARP-1 activity is
inhibited. NAD+, oxidized nicotinamide adenine
dinucleotide; NAFLD, non-alcoholic fatty liver disease; PARP-1,
poly(ADP-ribose) polymerase-1; PGC-1α, PPARγ coactivator-1α; PPARα,
peroxisome proliferator-activated receptor α; SIRT1, sirtuin 1.
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Copy and paste a formatted citation
Spandidos Publications style
Hu K, Tian H, Chen S, Liu Y, Wei R, Chen B and Jia Y: PARP‑1 in liver diseases: Molecular mechanisms, therapeutic potential and emerging clinical applications (Review). Mol Med Rep 32: 324, 2025.
APA
Hu, K., Tian, H., Chen, S., Liu, Y., Wei, R., Chen, B., & Jia, Y. (2025). PARP‑1 in liver diseases: Molecular mechanisms, therapeutic potential and emerging clinical applications (Review). Molecular Medicine Reports, 32, 324. https://doi.org/10.3892/mmr.2025.13689
MLA
Hu, K., Tian, H., Chen, S., Liu, Y., Wei, R., Chen, B., Jia, Y."PARP‑1 in liver diseases: Molecular mechanisms, therapeutic potential and emerging clinical applications (Review)". Molecular Medicine Reports 32.6 (2025): 324.
Chicago
Hu, K., Tian, H., Chen, S., Liu, Y., Wei, R., Chen, B., Jia, Y."PARP‑1 in liver diseases: Molecular mechanisms, therapeutic potential and emerging clinical applications (Review)". Molecular Medicine Reports 32, no. 6 (2025): 324. https://doi.org/10.3892/mmr.2025.13689
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Spandidos Publications style
Hu K, Tian H, Chen S, Liu Y, Wei R, Chen B and Jia Y: PARP‑1 in liver diseases: Molecular mechanisms, therapeutic potential and emerging clinical applications (Review). Mol Med Rep 32: 324, 2025.
APA
Hu, K., Tian, H., Chen, S., Liu, Y., Wei, R., Chen, B., & Jia, Y. (2025). PARP‑1 in liver diseases: Molecular mechanisms, therapeutic potential and emerging clinical applications (Review). Molecular Medicine Reports, 32, 324. https://doi.org/10.3892/mmr.2025.13689
MLA
Hu, K., Tian, H., Chen, S., Liu, Y., Wei, R., Chen, B., Jia, Y."PARP‑1 in liver diseases: Molecular mechanisms, therapeutic potential and emerging clinical applications (Review)". Molecular Medicine Reports 32.6 (2025): 324.
Chicago
Hu, K., Tian, H., Chen, S., Liu, Y., Wei, R., Chen, B., Jia, Y."PARP‑1 in liver diseases: Molecular mechanisms, therapeutic potential and emerging clinical applications (Review)". Molecular Medicine Reports 32, no. 6 (2025): 324. https://doi.org/10.3892/mmr.2025.13689
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