Cell migration switch

Epithelial-to-mesenchymal transition — the program by which orderly tissue cells turn migratory, driving fibrosis and organ scarring.

Cell fate signaling increases it.

EMT-and-invasion review 2013 — Notch signaling activates Snail/Slug/ZEB repressors of E-cadherin, driving epithelial-to-mesenchymal transition. PMID 24278531

Tissue renewal signaling increases it.

Lamouille 2014, Nat Rev Mol Cell Biol — canonical Wnt stabilizes β-catenin (via GSK3β inhibition), which engages TCF/LEF to induce the Snail/Twist EMT program. PMC4372086

Reduces scarring increases it.

Ramachandran 2018, eLife — tgf-β-induced epithelial-to-mesenchymal transition requires smad signaling (SMAD3 with SMAD1/5). Doi:10.7554/eLife.31756. TGF-beta is the most potent factor engaged to initiate and complete emt. emt and its reverse, met, both occur during physiological wound healing as well as pathological fibrosis — emt is not intrinsically pathological, and the same transition serves repair. doi 10.7554/eLife.31756.

It reduces Kidney.

Lovisa 2015, Nat Med 21:998 — tubular epithelial cells undergo a partial EMT program in renal fibrosis, arresting in G2 and downregulating solute transporters, causing parenchymal damage and loss of renal function. PMID 26236991

It reduces Sexual function.

Named across six reviews of endothelial dysfunction as part of the shared mechanism set: reduced nitric oxide availability, oxidative stress, inflammatory responses, apoptosis of endothelial cells, and the emerging concept of endothelial-mesenchymal transition. doi 10.3390/jcm15041621 · PMID 33923709 · PMC11988752

It increases Nerve protection.

Named across six reviews of endothelial dysfunction as part of the shared mechanism set: reduced nitric oxide availability, oxidative stress, inflammatory responses, apoptosis of endothelial cells, and the emerging concept of endothelial-mesenchymal transition. doi 10.3390/jcm15041621 · PMID 33923709 · PMC11988752

It reduces Strengthens veins.

Named across six reviews of endothelial dysfunction as part of the shared mechanism set: reduced nitric oxide availability, oxidative stress, inflammatory responses, apoptosis of endothelial cells, and the emerging concept of endothelial-mesenchymal transition. doi 10.3390/jcm15041621 · PMID 33923709 · PMC11988752

It increases Clears blocked nose & sinuses.

This is the same axis as eczema, and it splits the same way: type 2 endotypes are IL-4/IL-5/IL-13-driven and eosinophilic, while non-type-2 endotypes ARE driven by increased Th1 and Th17 responses, resulting in elevated neutrophil levels. Two endotypes, two cell types, two nodes. And the intervention evidence is unusually direct: dupilumab (IL-4Ralpha inhibitor) reduces polyp burden and restores smell, while MEPOLIZUMAB (anti-IL-5) and OMALIZUMAB (anti-IgE) address specific endotypes - three biologics, three targets, three endotype-matched responses. PMC11059040

It increases Eases allergy load.

This is the same axis as eczema, and it splits the same way: type 2 endotypes are IL-4/IL-5/IL-13-driven and eosinophilic, while non-type-2 endotypes ARE driven by increased Th1 and Th17 responses, resulting in elevated neutrophil levels. Two endotypes, two cell types, two nodes. And the intervention evidence is unusually direct: dupilumab (IL-4Ralpha inhibitor) reduces polyp burden and restores smell, while MEPOLIZUMAB (anti-IL-5) and OMALIZUMAB (anti-IgE) address specific endotypes - three biologics, three targets, three endotype-matched responses. PMC11059040

It increases Cellular aging.

Epithelial-mesenchymal transition and ECM stiffening - the altered mechanical properties hallmark. doi 10.1016/j.molmet.2023.101755 · PMC12293478

It reduces Gut barrier.

10.3389/fmed.2024.1368977 — The aging outcome lists the thirteen hallmarks themselves, each mapped to its pathway and labeled with its hallmark number. (from the reviews of this outcome). Verbatim: “In CD-associated intestinal fibrosis, epithelial-mesenchymal transition may serve as a source of new fibroblasts and consequently lead to overproduction of extracellular matrix”. doi 10.3389/fmed.2024.1368977

It reduces Skin.

Verbatim: “EMT may be involved in keloid generation and/or aggravation and may have potential as a keloid treatment target”. doi 10.1097/GOX.0000000000001138 · PMID 27975033 · PMC5142499

It reduces Gum health.

The one measured finding among them is the periodontal-anemia link: a meta-analysis of sixteen studies on hemoglobin and iron metabolism in periodontitis, whose authors call the association still controversial and ask for larger cohorts. (PMC7005133; doi 10.1152/japplphysiol.00971.2016; PMC12673670). Verbatim: “Both in vitro and in vivo data now support the potential involvement of EMT as a pathogenic mechanism in periodontal diseases which may facilitate bacterial invasion into the underlying gingival tissues and propagation of inflammation”. doi 10.1152/japplphysiol.00971.2016 · PMC7005133

It reduces Wound healing.

The one measured finding among them is the periodontal-anemia link: a meta-analysis of sixteen studies on hemoglobin and iron metabolism in periodontitis, whose authors call the association still controversial and ask for larger cohorts. doi 10.1152/japplphysiol.00971.2016 · PMC7005133

It increases Clear skin.

Drawn from reviews of neighboring outcomes rather than from studies of this outcome itself, which is weaker evidence, and the map marks it so. Sources: doi 10.3389/fmed.2025.1582946; PMC11897119; PMC11007107. doi 10.3389/fmed.2025.1582946 · PMC11897119

It reduces Supports airflow & lung function.

Verbatim: “This leads to reduced ciliated cells, goblet cell hyperplasia and increased epithelial mesenchymal transition, which contribute to impaired mucociliary clearance and airway remodelling”. doi 10.3389/fimmu.2023.1201658 · PMC10374037

It increases Stomach contents rising.

Drawn from reviews of neighboring outcomes rather than from studies of this outcome itself, which is weaker evidence, and the map marks it so. Sources: doi 10.1038/s41522-022-00352-6; PMC5559637. doi 10.1038/s41522-022-00352-6 · PMC5559637

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