In vitro expression of a 38,000 dalton heparin‐binding glycoprotein by morphologically differentiated smooth muscle cells

Abstract

In vitro, high density monolayer cultures of vascular smooth muscle cells can be induced to form multicellular nodules. The nodular cells appear to be morphologically differentiated smooth muscle cells. Sodium dodecyl sulfate (NaDodSO4)-polyacrylamide gel electrophoresis was used to compare the proteins synthesized and secreted by monolayer and nodular cultures of smooth muscle cells. Although most proteins appeared to be similar, the nodular cultures contained a unique heparin binding protein of Mr = 38,000 (38kD protein) (Millis, A.J.T., Hoyle, M., Reich, E., and Mann, D.M., 1985, J. Biol. Chem., 260:3754-3761). The 38kD protein was glycosylated and its apparent molecular weight was shifted to Mr = 32,500 after synthesis in the presence of tunicamycin or digestion with endoglycosidase F. The production of 38kD protein by nodular cell cultures did not appear to result from the degradation of a high molecular weight precursor in nodular conditioned medium. Further, it was not detected in monolayer cell conditioned medium that had been incubated with nodular cells. Finally, its synthesis was not induced in monolayer cell cultures that had been labeled in nodular cell conditioned medium. The 38kD protein appears to be uniquely associated with nodular cultures of smooth muscle cells.

YKL-40, a Marker of Inflammation and Endothelial Dysfunction, Is Elevated in Patients With Type 1 Diabetes and Increases With Levels of Albuminuria

“…It is a growth factor for several cell types and has an established role in extracellular matrix remodeling and angiogenesis (11). A substantial body of evidence indicates that YKL-40 participates in processes during the early stages of atherosclerosis, and it seems to be of pathogenic importance in the low-grade inflammation that precedes the development of cardiovascular disease (11)(12)(13)(14). We have previously found significantly elevated levels of YKL-40 in patients with type 2 diabetes and an independent positive correlation with insulin resistance and parameters of the lipid profile (15,16).…”

“…Studies show that YKL-40 plays a role in endothelial dysfunction in relation to cell migration, reorganization, and tissue remodeling during atherogenesis (12)(13)(14). YKL-40 promotes chemotaxis, cell attachment, spreading, and migration of vascular endothelial cells, suggesting that YKL-40 promotes the process of atherosclerotic plaque formation, in which vascular smooth muscle cells (VSMCs) are induced to migrate through the intima in response to exogenous signals (13).…”

Chitinase 3-like protein 2 (CHI3L2, YKL-39) activates phosphorylation of extracellular signal-regulated kinases ERK1/ERK2 in human embryonic kidney (HEK293) and human glioblastoma (U87 MG) cells

“…In human there are six proteins of this family [2], and two of them, macrophage chitotriosidase 1 (chiti nase 1, CHIT1) [3] and acidic mammalian chiti nase (AMCase) [4], are catalytically active chiti nases. Other chi lectins are chitinase 3 like 1 (CHI3L1) or human cartilage glycoprotein 39 (HC gp 39) or YKL 40 [5], chitinase 3 like 2 (CHI3L2) or YKL 39 [6], oviductin (oviductal glycoprotein, oviduct specific glycoprotein precur sor, estrogen dependent oviduct protein, mucin 9, OVGP1) [7] and less homologous chitinase like protein, which interacts with endocytic/sorting receptor stabilin 1 (stabilin 1 interacting chitinase like protein, SI CLP) [8].…”

“…YKL 40 monomer consists of 383 amino acids, contains signal peptide Met1-Ala21 for secretion and two structure domains [9]. N terminal amino acids of its mature form are tyrosine (Y), lysine (K), leucine (L) [5]. This lectin acts as a prolifera tive [10], anti apoptotic [11,12], migration and adhesion [13] factor, it enhances bacterial adhe sion to colonic epithelial cells through the interac tion with bacterial chitin binding protein [14].…”

Effect of moxonidine and amlodipine on serum YKL-40, plasma lipids and insulin sensitivity in insulin-resistant hypertensive patients—a randomized, crossover trial

“…[10][11][12][13][14] Although the physiological role of YKL-40 is unknown, the pattern of its expression in normal and disease states suggests a function in remodeling or degradation of the extracellular matrix. 13,14 YKL-40 is increasingly recognized as a marker of inflammation and endothelial dysfunction and it seems to be of pathogenic importance in the low-grade inflammation that may precede the development of cardiovascular disease.…”