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Published on: September 14, 2021
TGF-β1 signaling and Krüppel-like factor 10 regulate bone marrow-derived proangiogenic cell differentiation,
Akm Khyrul Wara1, ShiYin Foo, Kevin Croce
1Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Blood
|August 11, 2011
Summary
Krüppel-like factor 10 (KLF10) is crucial for proangiogenic cell (PAC) function and blood vessel repair after ischemia. Reduced KLF10 impairs PACs, highlighting its therapeutic potential for cardiovascular diseases.
Area of Science:
- Cardiovascular Biology
- Stem Cell Biology
- Molecular Medicine
Background:
- Proangiogenic cells (PACs) from bone marrow (BM) promote neovascularization in ischemic tissues.
- Common myeloid progenitors (CMPs) and granulocyte-macrophage progenitor cells (GMPs) are identified sources of PACs with angiogenic potential.
Purpose of the Study:
- To investigate the role of Krüppel-like factor 10 (KLF10) in PAC differentiation and function.
- To elucidate the mechanism by which KLF10 regulates PACs and their response to TGF-β1.
- To assess the clinical relevance of KLF10 in peripheral artery disease (PAD).
Main Methods:
- Expression analysis of KLF10 in PACs derived from CMPs and GMPs.
- Phenotypic and functional assessment of PACs in KLF10 knockout (KLF10(-/-)) mice.
- Hindlimb ischemia model in KLF10(-/-) mice to evaluate blood flow recovery.
- Rescue experiments using wild-type (WT) and KLF10(-/-) PACs.
- Overexpression studies of KLF10 in TGF-β1 signaling-impaired progenitors.
- Analysis of KLF10 expression in PACs from PAD patients.
Main Results:
- KLF10 is highly expressed in PACs derived from CMPs and GMPs, significantly higher than in other progenitors.
- KLF10(-/-) mice exhibit impaired PAC differentiation, TGF-β1 responsiveness, and reduced blood flow recovery after ischemia.
- WT PACs, but not KLF10(-/-) PACs, rescued the ischemic phenotype in KLF10(-/-) mice.
- KLF10 overexpression rescued PAC formation in TGF-β1(+/-) CMPs and GMPs.
- KLF10 directly targets the VEGFR2 promoter in PACs.
- KLF10 expression is reduced in PACs from PAD patients.
Conclusions:
- TGF-β1 signaling and KLF10 are critical regulators of functional PACs originating from CMPs and GMPs.
- KLF10 plays a key role in mediating PAC function and neovascularization, particularly under ischemic conditions.
- KLF10 represents a potential therapeutic target for cardiovascular ischemic diseases, including PAD.
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