Table 1.

Review of reported effects on the barrier function, such as proliferation, differentiation, and PM penetration in varying skin models upon exposure to PM

Model	PM type	Dose and application	Exposure time	Main findings	Ref.
Ex vivo human skin	SRM® 1649b	2 mg/cm2, topical	24 h	- Pyknotic nuclei. - Decreased collagen-1 protein expression.	[119]
Pig	SRM® 1648a and 1649b	100 μg/m2, topical	5 d	- Decreased E-cadherin, cytokeratin, and filaggrin protein expression.	[120]
Mice, BALB/c with disrupted barrier	PM ≤1 μm from Seoul, Korea	8 μg/cm2, topical	6 h and 2 w repetitive exposures, 10 times total	- Healthy barrier: PM remained in follicles. - Disrupted barrier: penetration of PM in SS. - Repeated exposure: dermal penetration of PM.	[121]
Mice, BALB/c	SRM® 1649b	100 μg/m2, topical	24 h repetitive exposures, 5 d total	- Decreased filaggrin protein expression.	[122]
Mice, HR-1	SRM® 1650b	100 μg/mL, topical	7 d	- PM internalization.	[123]
	SRM® 1650b	100 μg/mL, topical	7 d	- Increased keratin 10 and PCNA protein expression.	[124]
HSE	SRM® 2975	200 μg/mL, systemic	2 d repetitive exposures, 6 d total	- Decreased keratin 16, keratin 17, and Ki67 protein expression.	[125]
	ERM-CZ120	200 μg/mL, systemic	48 h	- Altered morphology of epidermis.	[126]
HEE	Diesel PM or vapor	0.05% (v/v), systemic	20 d	- Decreased protein expression of cornifin A, suprabasin, and antileukoproteinase.	[127]
	CAPs, PM2.5	0.5 and 2.0 μg/cm2, topical	24 and 48 h	- PM penetration in SC after 24 h. - PM penetration in deeper layers after 48 h. - No alterations in morphology.	[128]
	CRM no. 28	25 mg, topical	6 h	- Claudin 4 gene expression is upregulated. - No changes in mRNA expression of filaggrin, loricrin, involucrin, transglutaminase 1, keratin 1, keratin 10, keratin 5, and keratin 14.	[129]
	SRM® 1648a	200 ppm, systemic	96 h	- Altered morphology. - Decreased PCNA and filaggrin protein expression.	[130]
	SRM® 1648a	2.2, 8.9, and 17.9 μg/cm2, topical	24 and 48 h	- Decreased cytokeratin 10, involucrin, and loricrin protein expression. - Increased barrier permeability for 17.9 μg/cm2. - Increased protein expression of aquaporin 3.	[131]
	PM2.5 from Seoul, Korea	50 μg/mL, topical	24 h	- Decreased keratin-10, claudin-1, desmocollin-1, and IFN-γ protein expression. - Increased S100A7 and S100A8 protein expression.	[132]
	PM0.3–2.5 from Benin, West-Africa	30 μg/cm2, topical	24 h	- Decreased loricrin protein expression.	[133]
	PM2.5 from Xi’an, China	50 μg/mL, systemic	24 h repetitive exposures, 2, 4, or 6 d total	- Increased cholesterol levels. - Reduced squalene levels.	[134]
NHDF	SRM®2787	30 μg/cm2, systemic	24 h	- PM internalization into autolysosomes.	[135]
	ERM-CZ100	200 μg/mL, systemic	24 h	- Increased elastase and collagenase activity. - Increased procollagen protein expression.	[136]
	The pre-conditioned medium of HaCaT treated with CRM no. 28	125 μg/mL, systemic	30 m, 48 h post-incubation	- Increased elastase and collagenase activity.	[137]
NHEK	PM2.5 from Xi’an, China	50 μg/mL, systemic	24 h	- Top upregulated genes of transcriptomics analysis are S100A8, S100A9, keratin 6B, keratin 19, serpin B3, and mostly the genes are involved in cholesterol metabolism.	[134]
	Diesel PM or vapor	0.05% (v/v), systemic	20 d	- Decreased envoplakin, suprabasin, filaggrin, involucrin, sciellin, caspase-14, cornifin-A protein, keratin-1, and keratin-10 protein expression.	[127]
	Diesel PM	30 and 60 μg/mL, systemic	24 h	- PM internalization.	[138]
	Asian dust storm particles from Seoul, Korea	25 μg/mL, systemic	24 h	- Increased caspase 14 and ITGA6 mRNA expression.	[139]
	PM ≤1 μm from Seoul, Korea	40 μg/cm2, systemic	24 h	- PM internalization.	[121]
	PM2.5 from Seoul, Korea	50 μg/mL, systemic	2 or 4 d	- Decreased number and length of cilia. - Increased SPRR3 protein expression. - Decreased keratin 1, keratin 10, and IFT88 mRNA expression.	[140]
	SRM®2786	1 mg/mL, systemic	6 h	- RNA-Seq analysis: Upregulation of keratin-associated protein 2–3, keratin 13, keratin 34, and claudin 4. Downregulation of growth differentiation factor 15.	[141]
	PM2.5 from Seoul, Korea	25 μg/mL, systemic	24 h	- Top upregulated genes from transcriptomics analysis are SPRR family members and other cornified envelope-related genes, transglutaminase 3, involucrin, filaggrin, keratin 10, keratin 15, S100A7, S100A8, S100A9, and S10012.	[132]
HaCaT	CRM no. 28	125 μg/mL, systemic	30 m, 24 h post-incubation	- Increased elastase and collagenase activity.	[137]
	SRM® 1649b	50 μg/cm2, systemic	24 h	- Decreased aquaporin-3 protein expression.	[142]
	SRM® 1649b	50 μg/cm2, systemic	24 h	- Decreased filaggrin, repetin, involucrin, and loricrin protein expression after 24 h.	[143]
	PM2.5 from Shanghai, China	10–100 μg/mL, systemic	24 h	- Increased involucrin, repetin, and filaggrin (highest dose) protein expression. - No changes in loricrin protein expression.	[144]
	SRM® 1649b	25 and 50 μg/cm2, systemic	4 and 24 h	- Decreased filaggrin protein expression.	[122]
	SRM® 1650b	50 μg/mL, systemic	1, 4, 8, 12, and 24 h	- PM internalization.	[123]
	SRM® 2975	100 and 200 μg/mL, systemic	24 h	- No changes in loricrin protein expression. - Increased involucrin protein expression. - Decreased keratin 16, keratin 17, and Ki67 protein expression. - Decreased BrdU incorporation.	[125]
	CAPs, PM2.5	5–25 μg/mL, systemic	1, 3, 6, and 24 h	- PM internalization.	[145]

Abbreviations: w, week; d, day; h, hour; m, minute; HSE, human skin equivalent; HEE, human epidermal equivalent; NHEK, normal human epidermal keratinocyte; SRM, standard reference material; PM, particulate matter; CAP, concentrated ambient particles; SS, stratum spinosum; ppm, parts per million; CRM, certified reference material; BrdU, 5-bromo-2′-deoxyuridine