Thrombospondins Differentially Regulate Proteins Involved in Arterial Remodeling

Abstract

Thrombospondins (TSPs) are matricellular glycoproteins expressed in response to vascular injury. TSP-1 and TSP-2 are promotors of arterial remodeling while TSP-5 is believed to be protective. The current study assessed the differential effect of TSPs on protein expression in vascular smooth muscle cells (VSMCs). We hypothesized that TSP-1, TSP-2 and TSP-5 would regulate VSMC proteins involved in arterial remodeling. Human VSMCs were exposed to TSP-1, -2, -5 or serum free media (24 hours). Cell lysates were used to assess the targets TSP-1, TSP-2, TSP-5 and CD44), while the culture media was used to detect TGF-β1, PDGF-BB, ANGPTL-4 and IL-8. Statistical analysis was performed by t-test and p< 0.05 was considered significant. All TSPs increased their own expression and TSP-5 increased TSP-2. TSP-1 and TSP-2 increased production of ANGPTL-4 and PDGF-BB, while TSP-5 only increased ANGPTL-4. TSP-1 increased exclusively TGF-β1 and CD44 production. TSP-2 increased TSP-1 expression. All TSPs decreased IL-8. The findings suggest that TSP-1 and TSP-2 may promote vascular remodeling, in part, by increasing ANGPTL-4, PDGF-BB and their own expression. TSP-5 did not upregulate the inflammatory mediators TSP-1, PDGF-BB or TGF-β1, but upregulated its own expression, which could be a protective mechanism against the response to vascular injury.

Thrombospondin-2 holds prognostic value and is associated with metastasis and the mismatch repair process in gastric cancer

“…Its spatial structure is relatively stable, and TSP participates in the communication between cells and the intercellular matrix. Its main functions involve early embryonic development, damage repair, and tumorigenesis [ 10 , 11 ]. The molecular weight of TSP2 is approximately 145 kD; it is a trimeric structure sensitive to Ca2+ and maintained by disulphide bonds.…”

Nicotine in Senescence and Atherosclerosis

“…Furthermore, histological examination of aortic wall remodeling by nicotine by Rodella et al [133] indicated a significant upregulation of thrombospondin-1 (TSP-1), TGF-β1, plasminogen activator inhibitor-1 (PAI-1), and CD31 levels in VSMCs in the media in response to 100 µg/mL nicotine in drinking water. TSP-1 is a glycoprotein secreted by VSMCs in response to injury that mediates VSMC proliferation and migration [134] and arterial remodeling [135]. PAI-1, on the other hand, promotes the migration of VSMC by binding to the low-density lipoprotein receptor-related protein (LRP) [136].…”

Thrombospondin-2 Holds Prognostic Values and is Associated with the Metastasis and Mismatch Repair Process in Gastric Cancer

“…Its spatial structure is relatively stable, and it participates in the communication between cells and the intercellular matrix. Its main functions involve early embryonic development, damage repair, and tumorigenesis [10,11]. The molecular weight of TSP2 is about 145kD; it is a trimeric structure sensitive to Ca2 + and maintained by disul de bonds.…”