FIGURE 6.

Kallikrein (KLK) drives inflammation status in the severely cardiotoxic patient group (SP) through activated protease‐activated receptor 2 (PAR2). (A) Proposed KLK‐PAR2‐MAPK and ErbB signaling pathways in the patient‐specific induced pluripotent stem cell‐derived cardiomyocyte (pt‐iPSC‐CM) model. Pathways validated in this study are shown as dotted lines. (B, C) KLK5 and KLK8 levels detected in culture supernatant of pt‐iPSC‐CMs, as measured by ELISA. (D) Representative western blot analysis of PAR2 protein expression. (E) Quantification of PAR2 normalized to GAPDH. (F) PAR2 signaling assessed by Ca²⁺ transients induced by trypsin, a PAR2 agonist. (G, H) Representative western blot and quantification of p‐ERK1/2 and ERK1/2. (I, J) Representative western blot and quantification of p‐JNK and JNK protein expression. Data were obtained using pt‐iPSC‐CMs from six individuals, assays were repeated three to five times for ELISA and Ca²⁺ transients and twice for western blots. All data are expressed as mean ± SEM. NRG‐1, neuregulin‐1; SP, severely cardiotoxic patient group