Figure 2. p16Ink4a RNA-ISH transcription is upregulated in dermal tissues in chronic wounds. Representative RNA-ISH images showing p16Ink4a nuclear localization in (A) normal skin, (B) an acute wound, and (C) a chronic wound, 20× magnification (top) and focused zoom (bottom) (n = 6 in each group at day 14). (D) Quantification of p16Ink4a positive cells in epidermis, papillary dermis, and reticular dermis. Measurements are expressed as mean ± SEM. Statistical analysis was performed using Student’s t-test; ***p < 0.001, ****p < 0.0001. RNA-ISH, RNA in situ hybridization.