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. 2022 Feb 28;18(5):2047–2059. doi: 10.7150/ijbs.69343

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HB-EGF induces estrogen secretion and GCs apoptosis via cAMP-PKA-JNK/ERK-Ca²⁺-FOXO1 pathway. A, HB-EGF enhanced the expression of JNK and ERK via cAMP-PKA signaling. N = 3. B and C, HB-EGF induced estrogen secretion (N = 9) and CYP19A1 expression (N = 4) via JNK/ERK-Ca²⁺-FOXO1 pathway. SP, SP600125; GDC, GDC-0994; BAPTA, BAPTA-AM; AS, AS1842856. D, HB-EGF induced GCs apoptosis via JNK/ERK-Ca²⁺-FOXO1 pathway. N = 3. E-G, HB-EGF raised the expression or activity of CASP3 and BAX through JNK/ERK-Ca²⁺-FOXO1 pathway. N = 3. H-J, HB-EGF enhanced intracellular Ca²⁺ content via cAMP-PKA-ERK/JNK pathway. N = 3. K, Luciferase activity was assessed after GCs were transfected with pGL6-CYP19A1 plasmid and then treated with rHB-EGF in the absence or presence of FOXO1 inhibitor AS1842856. N = 6. L-N, HB-EGF increased FOXO1 expression via cAMP-PKA- JNK/ERK-Ca²⁺ pathway. N = 3.