Table 1. Inflammatory diseases... | Rockefeller University Press

Table 1.

Inflammatory diseases associated with mechanical dysregulation

Disease	Mechanical dysregulation	Cell types involved	Mechanotransducers	Inflammatory pathways and mediators	Pathophysiological outcomes	Relevant literature
Barrier tissue dysfunctions
Asthma	Bronchoconstriction-induced compression; excess cell extrusion	Airway epithelial cells; ILC2	PIEZO1	Damage-associated inflammatory signaling	Airway denudation; mucus hypersecretion; immune cell infiltration; barrier dysfunction	Bagley et al. (2024), Grainge et al. (2011), Kılıç et al. (2020), Mwase et al. (2025), Hurrell et al. (2024), and Lim et al. (2025)
VILI	Excessive mechanical stretch; high tidal volume and pressure; cyclical strain	Alveolar epithelial cells; endothelial cells; alveolar macrophages	TRPV4; PIEZO1	NLRP3 inflammasome activation; pro-inflammatory cytokine release	Barrier failure; pulmonary edema; acute lung inflammation and injury	Hamanaka et al. (2007), Wu et al. (2013), Michalick et al. (2017), Pairet et al. (2018), Solis et al. (2019), Bobba et al. (2021), and Li et al. (2024b)
IBD	Excess cell extrusion; mechanical stretch from peristalsis and obstruction; stiffened inflamed tissue	Intestinal epithelial cells; smooth muscle cells; Tregs	RAC1; cytoskeleton	Mucosal inflammation; mechanoregulation of immune cell migration and tissue egress	Barrier failure and dysregulated immune responses	Lin et al. (2014), Kim et al. (2016), Stewart et al. (2018), Chang et al. (2019a), Martínez-Sánchez et al. (2023), and Ullrich et al. (2023)
Inflammatory skin and eye conditions	Mechanical stretch; excessive tension, compression, and friction	Keratinocytes; mast cells; conjunctival epithelial cells	PIEZO1; cytoskeleton	Psoriatic inflammation and cytokine production; mast cell reprogramming; neutrophil infiltration	Epidermal hyperproliferation; barrier dysfunction; eczema susceptibility	Qiao et al. (2019), Serhan et al. (2025), and Fukuoka et al. (2025)
Stromal inflammation
Fibrosis (multiple organs)	Increased tissue stiffness; ECM remodeling	Fibroblasts; macrophages; dendritic cells	YAP/TAZ; PIEZO1; integrins; cytoskeleton	Fibroblast–immune feedback loops	Persistent inflammation; amplified fibrotic remodeling	Pakshir et al. (2019), Meli et al. (2020), Chakraborty et al. (2021a), Zhou et al. (2022), and Ezzo et al. (2024)
Pulmonary fibrosis	Repetitive mechanical stretch; increased tissue stiffness	Mast cells; macrophages; fibroblasts	Integrins; cytoskeleton	Mast cell degranulation; TGF-β1 signaling	ECM accumulation; loss of lung compliance	Shimbori et al. (2019), Xu et al. (2024), and Zhang et al. (2026)
Liver fibrosis	Increased tissue stiffness	Hepatocytes; macrophages (Kupffer cells); hepatic stellate cells	PIEZO1 YAP	Enhanced efferocytosis upon PIEZO1 activation (Kupffer cells); lipogenesis (hepatocytes)	Clearance of apoptotic cells, fibrotic resolution (mechano-inflammatory feedback in Kupffer cells); MASLD progression	Georges et al. (2007), Olsen et al. (2011), Mitten and Baffy (2022), Greuter et al. (2022), Luo et al. (2023), Wang et al. (2024), and Ma et al. (2026)
Cutaneous fibrosis	Persistent tensile strain and pressure; ECM remodeling; wound contracture	Fibroblasts; keratinocytes; dendritic cells	FAK; integrins; cytoskeleton; MAPK/ERK	NF-κB activation; NRF2-mediated regulation of inflammation	Excess ECM deposition; fibroblast persistence; chronic inflammatory scarring	Wong et al. (2012), Nakasaki et al. (2015), Chen et al. (2021), Chen et al. (2022), Chen et al. (2025a), and Chaudhary et al. (2025)
Cardiac fibrosis	Pathological mechanical loading; increased stiffness	Myofibroblasts	Integrins; cytoskeleton PIEZO1	Inflammatory and profibrotic transcriptional programs	Collagen deposition; myocardial stiffening; impaired cardiac function	Blythe et al. (2019) and Cho et al. (2025)
Myelofibrosis (bone marrow)	Tissue stiffening; mechanical constraint of hematopoietic cells	Monocytes	Cytoskeleton; TRPV4	Myeloid-specific PI3K-γ signaling	Monocytosis (pathological monocyte differentiation and pro-inflammatory activation)	Vining et al. (2022)
PAS	Uterine scar matrix–induced tissue stiffening	Decidual stromal cells (fibroblasts)	PIEZO1	NF-κB activation; pro-inflammatory cytokine release (IL-8 and G-CSF)	Pathological placental trophoblast invasion; sustained inflammation	Wenqiang et al. (2024)
Aging	ECM remodeling, altered stiffness, viscoelasticity, and force transmission	Stromal cells; immune cells; stem cells; nucleus pulposus cells	Nucleus (LINC, lamin A/C, chromatin); YAP/TAZ; PIEZO1	cGAS–STING activation; SASP	Cellular senescence; inflammaging; degenerative tissue remodeling	Sladitschek-Martens et al. (2022), Wu et al. (2022), De Silva et al. (2023), Li et al. (2025), Mejía-Ramírez et al. (2025), Shang et al. (2026)
Obesity and metabolic diseases	ECM remodeling; increased adipose tissue stiffness and tension	Adipocytes; macrophages; fibroblasts	YAP/TAZ; integrins; cytoskeleton	Chronic adipose inflammation; SASP; tumor-associated macrophage phenotypes	Metabolic dysfunction; impaired thermogenesis; cancer-promoting microenvironment	Pellegrinelli et al. (2014), Pellegrinelli et al. (2023), Rabhi et al. (2022), Springer et al. (2019), Seo et al. (2015), and Incio et al. (2016)
Osteoarthritis	Excessive mechanical loading; ECM remodeling, stiffening, and cross-linking	Chondrocytes; synovial fibroblasts; macrophages	PIEZO1/2; integrins; cytoskeleton; RhoA-ROCK2 signaling	NF-κB, TGF-β, cGAS–STING, and complement activation; monocyte recruitment	Cell death; cartilage degeneration; osteoclast differentiation; bone erosion	Lee et al. (2014), Lee et al. (2017), Lee et al. (2021), Kim et al. (2015), Chang et al. (2019b), Zhen et al. (2021), Cambré et al. (2018), Cambré et al. (2019), Dudek et al. (2023), and Xu et al. (2025a)
Circulatory system diseases
Atherosclerosis	Disturbed flow; oscillatory shear stress; increased vascular stiffness; hypertensive pressure	Endothelial cells; VSMCs; macrophages (foam cells)	Junctional complex; YAP/TAZ; caveolae; glycocalyx; TRPV4; PIEZO1	NF-κB, JNK, and inflammasome activation; eNOS downregulation; metabolic rewiring; lipid droplet accumulation	Vascular inflammation; reduced vasodilation; monocyte recruitment; foam cell formation; plaque development	Tzima et al. (2005), Baeyens et al. (2014), Wang et al. (2016a), Wang et al. (2016b), Albarrán-Juárez et al. (2018), Ramírez et al. (2019), Atcha et al. (2024), Swiatlowska et al. (2022), and Swiatlowska et al. (2024)
Heart disease	Altered myocardial load; tissue strain after injury	Macrophages; neurons; fibroblasts; cardiomyocytes	PIEZO1; cytoskeleton	Neurogenic inflammation; macrophage-mediated inflammatory remodeling	Impaired ventricular remodeling, coronary angiogenesis, and heart failure progression	Baratchi et al. (2020), Wong et al. (2021), Zhong et al. (2023), Sun et al. (2024), Cho et al. (2025), and Li et al. (2026)
Blood disorders	Altered cell rigidity and deformability; shear stress	Erythrocytes; endothelial cells; neutrophils	PIEZO1; cytoskeleton	Hyperactivation of phagocytosis; endothelial activation; NETosis	Anemia; impaired vascular remodeling; thrombosis	Sosale et al. (2015), Lasch et al. (2019), Caruso et al. (2022), and Caruso et al. (2024)

Disease	Mechanical dysregulation	Cell types involved	Mechanotransducers	Inflammatory pathways and mediators	Pathophysiological outcomes	Relevant literature
Barrier tissue dysfunctions
Asthma	Bronchoconstriction-induced compression; excess cell extrusion	Airway epithelial cells; ILC2	PIEZO1	Damage-associated inflammatory signaling	Airway denudation; mucus hypersecretion; immune cell infiltration; barrier dysfunction	Bagley et al. (2024), Grainge et al. (2011), Kılıç et al. (2020), Mwase et al. (2025), Hurrell et al. (2024), and Lim et al. (2025)
VILI	Excessive mechanical stretch; high tidal volume and pressure; cyclical strain	Alveolar epithelial cells; endothelial cells; alveolar macrophages	TRPV4; PIEZO1	NLRP3 inflammasome activation; pro-inflammatory cytokine release	Barrier failure; pulmonary edema; acute lung inflammation and injury	Hamanaka et al. (2007), Wu et al. (2013), Michalick et al. (2017), Pairet et al. (2018), Solis et al. (2019), Bobba et al. (2021), and Li et al. (2024b)
IBD	Excess cell extrusion; mechanical stretch from peristalsis and obstruction; stiffened inflamed tissue	Intestinal epithelial cells; smooth muscle cells; Tregs	RAC1; cytoskeleton	Mucosal inflammation; mechanoregulation of immune cell migration and tissue egress	Barrier failure and dysregulated immune responses	Lin et al. (2014), Kim et al. (2016), Stewart et al. (2018), Chang et al. (2019a), Martínez-Sánchez et al. (2023), and Ullrich et al. (2023)
Inflammatory skin and eye conditions	Mechanical stretch; excessive tension, compression, and friction	Keratinocytes; mast cells; conjunctival epithelial cells	PIEZO1; cytoskeleton	Psoriatic inflammation and cytokine production; mast cell reprogramming; neutrophil infiltration	Epidermal hyperproliferation; barrier dysfunction; eczema susceptibility	Qiao et al. (2019), Serhan et al. (2025), and Fukuoka et al. (2025)
Stromal inflammation
Fibrosis (multiple organs)	Increased tissue stiffness; ECM remodeling	Fibroblasts; macrophages; dendritic cells	YAP/TAZ; PIEZO1; integrins; cytoskeleton	Fibroblast–immune feedback loops	Persistent inflammation; amplified fibrotic remodeling	Pakshir et al. (2019), Meli et al. (2020), Chakraborty et al. (2021a), Zhou et al. (2022), and Ezzo et al. (2024)
Pulmonary fibrosis	Repetitive mechanical stretch; increased tissue stiffness	Mast cells; macrophages; fibroblasts	Integrins; cytoskeleton	Mast cell degranulation; TGF-β1 signaling	ECM accumulation; loss of lung compliance	Shimbori et al. (2019), Xu et al. (2024), and Zhang et al. (2026)
Liver fibrosis	Increased tissue stiffness	Hepatocytes; macrophages (Kupffer cells); hepatic stellate cells	PIEZO1YAP	Enhanced efferocytosis upon PIEZO1 activation (Kupffer cells); lipogenesis (hepatocytes)	Clearance of apoptotic cells, fibrotic resolution (mechano-inflammatory feedback in Kupffer cells); MASLD progression	Georges et al. (2007), Olsen et al. (2011), Mitten and Baffy (2022), Greuter et al. (2022), Luo et al. (2023), Wang et al. (2024), and Ma et al. (2026)
Cutaneous fibrosis	Persistent tensile strain and pressure; ECM remodeling; wound contracture	Fibroblasts; keratinocytes; dendritic cells	FAK; integrins; cytoskeleton; MAPK/ERK	NF-κB activation; NRF2-mediated regulation of inflammation	Excess ECM deposition; fibroblast persistence; chronic inflammatory scarring	Wong et al. (2012), Nakasaki et al. (2015), Chen et al. (2021), Chen et al. (2022), Chen et al. (2025a), and Chaudhary et al. (2025)
Cardiac fibrosis	Pathological mechanical loading; increased stiffness	Myofibroblasts	Integrins; cytoskeletonPIEZO1	Inflammatory and profibrotic transcriptional programs	Collagen deposition; myocardial stiffening; impaired cardiac function	Blythe et al. (2019) and Cho et al. (2025)
Myelofibrosis (bone marrow)	Tissue stiffening; mechanical constraint of hematopoietic cells	Monocytes	Cytoskeleton; TRPV4	Myeloid-specific PI3K-γ signaling	Monocytosis (pathological monocyte differentiation and pro-inflammatory activation)	Vining et al. (2022)
PAS	Uterine scar matrix–induced tissue stiffening	Decidual stromal cells (fibroblasts)	PIEZO1	NF-κB activation; pro-inflammatory cytokine release (IL-8 and G-CSF)	Pathological placental trophoblast invasion; sustained inflammation	Wenqiang et al. (2024)
Aging	ECM remodeling,altered stiffness, viscoelasticity, and force transmission	Stromal cells; immune cells; stem cells; nucleus pulposus cells	Nucleus (LINC, lamin A/C, chromatin);YAP/TAZ; PIEZO1	cGAS–STING activation; SASP	Cellular senescence; inflammaging; degenerative tissue remodeling	Sladitschek-Martens et al. (2022), Wu et al. (2022), De Silva et al. (2023), Li et al. (2025), Mejía-Ramírez et al. (2025), Shang et al. (2026)
Obesity and metabolic diseases	ECM remodeling; increased adipose tissue stiffness and tension	Adipocytes; macrophages; fibroblasts	YAP/TAZ; integrins; cytoskeleton	Chronic adipose inflammation; SASP; tumor-associated macrophage phenotypes	Metabolic dysfunction; impaired thermogenesis; cancer-promoting microenvironment	Pellegrinelli et al. (2014), Pellegrinelli et al. (2023), Rabhi et al. (2022), Springer et al. (2019), Seo et al. (2015), and Incio et al. (2016)
Osteoarthritis	Excessive mechanical loading; ECM remodeling, stiffening, and cross-linking	Chondrocytes; synovial fibroblasts; macrophages	PIEZO1/2; integrins; cytoskeleton; RhoA-ROCK2 signaling	NF-κB, TGF-β, cGAS–STING, and complement activation; monocyte recruitment	Cell death; cartilage degeneration; osteoclast differentiation; bone erosion	Lee et al. (2014), Lee et al. (2017), Lee et al. (2021), Kim et al. (2015), Chang et al. (2019b), Zhen et al. (2021), Cambré et al. (2018), Cambré et al. (2019), Dudek et al. (2023), and Xu et al. (2025a)
Circulatory system diseases
Atherosclerosis	Disturbed flow; oscillatory shear stress; increased vascular stiffness; hypertensive pressure	Endothelial cells;VSMCs; macrophages (foam cells)	Junctional complex; YAP/TAZ; caveolae; glycocalyx; TRPV4; PIEZO1	NF-κB, JNK, and inflammasome activation; eNOS downregulation; metabolic rewiring; lipid droplet accumulation	Vascular inflammation; reduced vasodilation; monocyte recruitment; foam cell formation; plaque development	Tzima et al. (2005), Baeyens et al. (2014), Wang et al. (2016a), Wang et al. (2016b), Albarrán-Juárez et al. (2018), Ramírez et al. (2019), Atcha et al. (2024), Swiatlowska et al. (2022), and Swiatlowska et al. (2024)
Heart disease	Altered myocardial load; tissue strain after injury	Macrophages; neurons; fibroblasts; cardiomyocytes	PIEZO1; cytoskeleton	Neurogenic inflammation; macrophage-mediated inflammatory remodeling	Impaired ventricular remodeling, coronary angiogenesis, and heart failure progression	Baratchi et al. (2020), Wong et al. (2021), Zhong et al. (2023), Sun et al. (2024), Cho et al. (2025), and Li et al. (2026)
Blood disorders	Altered cell rigidity and deformability; shear stress	Erythrocytes; endothelial cells; neutrophils	PIEZO1; cytoskeleton	Hyperactivation of phagocytosis; endothelial activation; NETosis	Anemia; impaired vascular remodeling; thrombosis	Sosale et al. (2015), Lasch et al. (2019), Caruso et al. (2022), and Caruso et al. (2024)

LINC, linker of nucleoskeleton and cytoskeleton; NRF2, nuclear factor erythroid 2-related factor 2.

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