Transforming growth factor-beta (TGF-beta) and its signaling mediators play crucial roles in vascular formation. Our previous microarray analysis identified monocyte chemoattractant protein-1 (MCP-1) as a TGF-beta target gene in endothelial cells (ECs). Here, we report that MCP-1 mediates the angiogenic effect of TGF-beta by recruiting vascular smooth muscle cells (VSMCs) and mesenchymal cells toward ECs. By using a chick chorioallantoic membrane assay, we show that TGF-beta promotes the formation of new blood vessels and this promotion is attenuated when MCP-1 activity is blocked by its neutralizing antibody. Wound healing and transwell assays established that MCP-1 functions as a chemoattractant to stimulate migration of VSMCs and mesenchymal 10T1/2 cells toward ECs. Furthermore, the conditioned media from TGF-beta-treated ECs stimulate VSMC migration, and inhibition of MCP-1 activity attenuates TGF-beta-induced VSMC migration toward ECs. Finally, we found that MCP-1 is a direct gene target of TGF-beta via Smad3/4. Taken together, our findings suggest that MCP-1 mediates TGF-beta-stimulated angiogenesis by enhancing migration of mural cells toward ECs and thus promoting the maturation of new blood vessels.
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http://dx.doi.org/10.1182/blood-2006-07-036400 | DOI Listing |
Nat Commun
January 2025
The Department of Urology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, 200233, China.
Balanced self-renewal and differentiation of stem cells are crucial for maintaining tissue homeostasis, but the underlying mechanisms of this process remain poorly understood. Here, from an RNA interference (RNAi) screen in adult Drosophila intestinal stem cells (ISCs), we identify a factor, Pax, which is orthologous to mammalian PXN, coordinates the proliferation and differentiation of ISCs during both normal homeostasis and injury-induced midgut regeneration in Drosophila. Loss of Pax promotes ISC proliferation while suppressing its differentiation into absorptive enterocytes (ECs).
View Article and Find Full Text PDFTaiwan J Obstet Gynecol
January 2025
Department of Pathology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, 23561, Taiwan; Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan. Electronic address:
Objective: Endometrial cancer (EC) shows substantial heterogeneity in their immune microenvironment. BHLHE22 is consistently hypermethylated in EC and high expression of BHLHE22 is likely to be immunosuppressive in the tumor microenvironment. Herein, we evaluated expression of BHLHE22, programmed cell death ligand-1 (PD-L1), CD8, CD68 and mismatch repair proteins in EC.
View Article and Find Full Text PDFiScience
January 2025
Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka, Japan.
Ischemia and pathological angiogenesis in retinal vascular diseases cause serious vision-related problems. However, the transcriptional regulators of vascular repair remain unidentified. Thus, the factors and mechanisms involved in angiogenesis must be elucidated to develop approaches for restoring normal blood vessels.
View Article and Find Full Text PDFCell Commun Signal
January 2025
School of Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Endothelial-mesenchymal transition (EndMT) is defined as an important process of cellular differentiation by which endothelial cells (ECs) are prone to lose their characteristics and transform into mesenchymal cells. During EndMT, reduced expression of endothelial adhesion molecules disrupts intercellular adhesion, triggering cytoskeletal reorganization and mesenchymal transition. Numerous studies have proved that EndMT is a multifaceted biological event driven primarily by cytokines such as TGF-β, TNF-α, and IL-1β, alongside signaling pathways like WNT, Smad, MEK-ERK, and Notch.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
Department of Physiology, Navy Medical University, Shanghai 200433, China. Electronic address:
In the mammalian cardiovascular system, endothelial glycocalyx is a gel-like layer that covers the luminal surface of endothelial cells (ECs) and plays crucial roles in vascular homeostasis, permeability and leukocyte adhesion. Degradation of this structure occurs early in sepsis and becomes accordingly dysfunctional. In severe cases, it is not self-regulated by the organism.
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