Dusp2-flox Mouse

Dusp2, a member of the mitogen-activated protein kinase phosphatase family, is involved in abolishing the activation of mitogen-activated protein kinases (MAPKs) [8]. It plays critical roles in immune processes, inflammatory responses, and cancer progression [8]. Associated pathways include the AKT1, MEK/ERK, P38 MAPK, and STAT3 pathways among others [1,2,3].

In pancreatic cancer, DUSP2 promotes apoptosis through recruiting CSNK2A1 to inhibit AKT1 phosphorylation under hypoxic conditions, and activation of AKT1 leads to DUSP2 degradation via the AKT1/TRIM21 loop [1]. In bladder cancer, its down-regulation is associated with poor prognosis, and overexpression inhibits cell proliferation, metastasis, and affects the immune microenvironment by regulating MEK/ERK and P38 MAPK through PTPN7 [2,8]. In lupus nephritis, DUSP2 reduces proteinuria, cytokine levels, and improves renal tissue injury by inhibiting STAT3 phosphorylation [3]. In zebrafish, DUSP2 deletion promotes Mauthner cell axonal regeneration at an early stage, possibly by enhancing JNK phosphorylation [4]. In acute kidney injury, DUSP2-STAT1 axis regulates renal tubular epithelial cell pyroptosis, with DUSP2 deletion promoting pyroptosis and DUSP2 overexpression ameliorating AKI [5]. In gastric cancer, exosomal miR-519a-3p activates the MAPK/ERK pathway by targeting DUSP2, causing M2-like macrophage polarization and promoting liver metastasis [6]. In high-glucose-induced vascular endothelial cell dysfunction, interfering with Dusp2 promotes cell functions and alleviates mouse diabetic hindlimb ischemia by promoting p38 MAPK pathway activation [7].

In conclusion, Dusp2 is a key regulator in multiple biological processes and diseases. Gene-knockout models, such as in zebrafish and mice, have been instrumental in revealing its functions in cancer, kidney diseases, and axonal regeneration. Understanding Dusp2's role provides potential therapeutic targets for various diseases, including pancreatic, bladder, and gastric cancers, as well as lupus nephritis and acute kidney injury.