The dynamic regulatory mechanisms and cell-type specificity of autophagy in PAH

The gap

Evidence profile

Sourced from the stated research gap and future work and conclusions of the source papers, classified as general, drawn from work published between 2024 and 2026, spanning 3 journals. Those papers have been cited 59 times in total.

Supporting evidence — 3 representative gaps

• Autophagy-Targeted Vascular Remodeling in Pulmonary Arterial Hypertension: Molecular Mechanisms and Therapeutic Perspectives (2026) · Journal of Cardiovascular Development and Disease · doi

  The paper identifies a gap in the understanding of the dynamic regulatory mechanisms and cell-type specificity of autophagy in PAH. There is a need to further elucidate the role of autophagy in PAH and to identify potential therapeutic strategies. The paper aims to address this gap by summarizing the molecular mechanisms linking autophagy to PAH and evaluating potential therapeutic strategies.

  generalstated research gap
  Keywords: paper identifies gap understanding dynamic regulatory mechanisms cell-type
• Autophagy in chronic rhinosinusitis with or without nasal polyps (2024) · Frontiers in Cell and Developmental Biology · cited 3× · doi

  From the overview above, autophagy displays both protective and detrimental effects on CRS. We speculate that autophagy is enhanced in the early stages of disease in CRS to remove cellular damage caused by pathogens or allergens to maintain organismal homeostasis, but as the damage persists, autophagy will be depleted and exhibit autophagic insufficiency. Current research leans towards autophagy deficiency in CRS, particularly in CRSwNP. However, the limited literature, small sample sizes in clinical studies, and scarcity of animal experiments highlight the need for further investigation. Studies have mainly focused on NFs from NPs tissues or control mucosa, as well as HNEpCs from healthy individuals, with conflicting findings on autophagy regulation. Most of the literature favors the presence of autophagy upregulation in HNEpCs and autophagy downregulation in NFs (Shun et al., 2016; Wang et al., 2017a; Wang et al., 2017b; Ye et al., 2019; Zhang et al., 2022). However, there is an exception which showed autophagy upregulation in NFs (Shun et al., 2016). Future in vitro experiments using both cell types could shed light on the differences in autophagy levels and their impact on CRS progression. The review focused on eCRS models, leaving room for further exploration of autophagy differences in non-eCRS models (Choi et al., 2018; Lee et al., 2022). Non-type 2 inflammation in CRS, represented by LPS, IFN-λ, and HNE-stimulated HNEpCs, often shows autophagy excess involving AMPK-mTOR, JNK–AP-1, and HNE-TRAF6 pathways (Wang et al., 2017a; Wang et al., 2017b; Ye et al., 2019). On the other hand, the PI3K/Akt/HIF-1α and COX-2/ HPGDS/PGD2 pathway tends to regulate type-2 inflammation in CRS, leading to autophagy deficiency (Choi et al., 2018; Cheng et al., 2022). Interestingly, no significant differences in autophagy marker expression were observed between eCRSwNP and non-eCRSwNP tissue samples, although further confirmation with larger sample sizes is warranted (Wang et al., 2017a; Wang et al., 2022). The dual role of autophagy in CRS may vary among different cell types, as seen in lung inflammation. Myeloid lineage cells (especially neutrophils and eosinophils) and lymphoid lineage cells (e.g., CD4+, CD8+, ILC2, and B-cells) can enhance lung inflammation through autophagy modulation in distinct pathways, while epithelial cells and fibroblasts can influence lung remodeling via autophagy regulation (Painter et al., 2020). As current in vitro studies mainly focus on non-immune cells (HNEpCs and NFs), additional experiments are needed to understand the changes in autophagy levels in immune cells of CRS. The development of personalized and autophagy modulators pathogenesis holds promise for future therapeutic interventions. tailored to specific types cell A recent study found that offspring of female mice exposed to OVA may reduce Th2 inflammation by enhancing autophagy in mast cells when exposed to OVA (Kim et al., 2021). Overexpression of Orosomucoid-like-3 (ORMDL3) increased the expression of SERCA2b, activating transcription factor 6 (ATF6), Beclin-1, and LC3BII. Conversely, inhibiting autophagy or knocking down ATF6 reversed the decrease in anaphylactic reaction caused by ORMDL3 overexpression (Li et al., 2021). Autophagy has also been linked to epithelial mesenchymal transition (EMT) and epigenetic changes in the fields of oncology, lung diseases, and diabetes (Ranieri et al., 2021; Zeng et al., 2021; Gundamaraju et al., 2022; Yu et al., 2024). Both EMT and epigenetic changes play roles in the pathogenesis of CRS (Li et al., 2022; Wang et al., 2023). These findings provide valuable insights for future research on CRS, further exploring the role of highlighting the importance of autophagy in this condition. While the current study is not without controversy, it sheds light on potential new therapeutic approaches for CRS by targeting autophagy.

  generalfuture workevidence 5/5
  Keywords: autophagy wang cells ammation further hnepcs lung ciency current experiments future cell types differences changes
• Molecular Mechanisms of Autophagy Decline during Aging (2024) · Cells · cited 56× · doi

  In particular, it remains unclear how a combination of multiple points of failure in autophagy with age drives the decline of the overall process during aging. Much work has already been carried out to investigate the consequences of modulating autophagy in model organisms or disease models, but whether these findings translate to aged humans remains unclear and is an important area for future research.

  generalconclusionsevidence 3/5
  Keywords: remains unclear autophagy particular combination multiple points failure drives decline overall process aging already carried

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