β-Catenin promotes long-term survival and angiogenesis of peripheral blood mesenchymal stem cells via the Oct4 signaling pathway

Abstract

Stem cell therapy has been extensively studied to improve heart function following myocardial infarction; however, its therapeutic potency is limited by low rates of engraftment, survival, and differentiation. Here, we aimed to determine the roles of the β-catenin/Oct4 signaling axis in the regulation of long-term survival and angiogenesis of peripheral blood mesenchymal stem cells (PBMSCs). These cells were obtained from rat abdominal aortic blood. We showed that β-catenin promotes the self-renewal, antiapoptotic effects, and long-term survival of PBMSCs by activating the Oct4 pathway through upregulation of the expression of the antiapoptotic factors Bcl2 and survivin and the proangiogenic cytokine bFGF and suppression of the levels of the proapoptotic factors Bax and cleaved caspase-3. β-Catenin overexpression increased Oct4 expression. β-Catenin knockdown suppressed Oct4 expression in PBMSCs. However, β-catenin levels were not affected by Oct4 overexpression or knockdown. Chromatin immunoprecipitation assays proved that β-catenin directly regulates Oct4 transcription in PBMSCs. In vivo, PBMSCs overexpressing β-catenin showed high survival in infarcted hearts and resulted in better myocardial repair. Further functional analysis identified Oct4 as the direct upstream regulator of Ang1, bFGF, HGF, VEGF, Bcl2, and survivin, which cooperatively drive antiapoptosis and angiogenesis of engrafted PBMSCs. These findings revealed the regulation of β-catenin in PBMSCs by the Oct4-mediated antiapoptotic/proangiogenic signaling axis and provide a breakthrough point for improving the long-term survival and therapeutic effects of PBMSCs.

Role of Protein Phosphatases in Tumor Angiogenesis: Assessing PP1, PP2A, PP2B and PTPs Activity

“…PTPRK specifically dephosphorylates EGFR, hence inhibiting cell proliferation and migration caused by EGF-induced EGFR-dependent signaling [242][243][244]. Besides EGFR, another identified substrate for PTPRK is β-catenin, which has undisputed role in angiogenesis [245][246][247]. PTPRK can be associated with neuropilin 1 (NRP1), a non-tyrosine kinase transmembrane glycoprotein.…”

Nkx2.5: a crucial regulator of cardiac development, regeneration and diseases

“…As an adhesive connexin, β-Catenin, together with e-cadherin and alpha Catenin, forms an adhesive connexin complex, which maintains normal tissue structure and morphogenesis by regulating cell growth and intercellular adhesion. In addition, β-Catenin is a key functional effector molecule downstream of the classical Wnt pathway, which is crucial in embryonic development, tissue homeostasis, and tumorigenesis and development ( 78 ). By attaching to the unique components of the β-Catenin promoter region, Nkx2.5 can control the expression of -Catenin, which results in Nkx2.5 implementing regulation of the Wnt signaling pathway ( 79 ).…”

A review on the molecular basis of stemness of mesenchymal stem cells

“…A 2022 paper established that β-catenin increased the survival of MSCs and promoted angiogenesis in the case of stem cell therapy for cardiac diseases. β-catenin positively regulates OCT4 which in turn regulates genes such as Ang1, bFGF, HGF, VEGF, Bcl2, and surviving which are responsible for the survival and angiogenesis of MSCs [19].…”