Klf9, or Krüppel-like factor 9, is a transcription factor that plays a crucial role in multiple biological processes. It is involved in regulating gene expression related to mitochondrial homeostasis, energy metabolism, oxidative stress response, and cell differentiation. Associated pathways include those related to PPARγ/NRF2, NF-κB, MAPK, and Notch1 signaling, among others. Genetic models, such as KO and CKO mouse models, have been instrumental in studying Klf9's functions [1-5, 7-10].

In cardiac-related studies, both global and cardiac-specific Klf9-deficient mice displayed hypertrophic cardiomyopathy. Klf9 knockout led to mitochondrial disarray, fragmentation, and impaired respiratory function in cardiomyocytes, along with inhibited mitophagy [1]. In diabetic cardiomyopathy, cardiac-specific overexpression of Klf9 deteriorated cardiac function, while silencing Klf9 alleviated cardiac dysfunction, hypertrophy, fibrosis, and the inflammatory response [2]. In the context of myocardial infarction, Klf9 deficiency protected the heart from inflammatory injury by inhibiting the activation of NF-κB and MAPK signaling in macrophages [3]. In dental stem cells, Klf9 depletion promoted proliferation but suppressed osteogenic differentiation, while its overexpression had the opposite effect, and it regulated this through negatively modulating the Notch1-mediated signaling pathway [4]. In mesenchymal stem cells, depletion of Klf9 compromised their osteogenic differentiation ability [5].

In summary, Klf9 is essential for maintaining mitochondrial homeostasis in the heart, regulating the inflammatory response in cardiovascular diseases, and controlling osteogenic differentiation in stem cells. The use of Klf9 KO/CKO mouse models has significantly contributed to understanding its role in cardiac-related diseases, diabetes-associated cardiomyopathy, and stem-cell-based osteogenesis.