Hypothalamic Proline-Rich Polypeptide Enhances Bone Marrow Colony-Forming Cell Proliferation and Stromal Progenitor Cell Differentiation

Abstract

The AGAPEPAEPAQPGVY proline-rich peptide (PRP-1) was isolated from neurosecretory granules of the bovine neurohypophysis; it is produced by N. supraopticus and N. paraventricularis. It has been shown that PRP-1 has many potentially beneficial biological effects, including immunoregulatory, hematopoietic, antimicrobial, and antineurodegenerative properties. Here we showed that PRP increased colony-forming cell (CFC) proliferation in rat bone marrow (BM) cells in vivo. In PRP-treated rat BM, the CFU number at day 7 and day 14 was considerably increased in comparison with untreated rat BM and no difference was found at day 21 and day 28. The related peptide [arg 8 ]vasopressin did not reveal CFC proliferation. PRP failed to farther increase CFC proliferation in vitro in BM obtained from PRP-treated or untreated rats. After 3-4 days of human BM stromal cell cultivation in the presence of 2-20 µg/ml PRP the appearance of cells expressing CD15, CD10, CD11a, CD11b, CD3, CD4, and CD16 surface antigens did not differ from the untreated cells. PRP increased the appearance of CD14-positive cells upon 3-4-day incubation with both adult and fetal BM stromal cells. Our results suggest a previously undescribed role for the hypothalamic peptide within neurosecretory hypothalamus-bone marrow humoral axis, because PRP enhances BM colonyforming cell proliferation and stromal cell differentiation.

Proline-Rich Hypothalamic Polypeptide Has Opposite Effects on the Proliferation of Human Normal Bone Marrow Stromal Cells and Human Giant-cell Tumour Stromal Cells

“…The regulating effect of PRP on myelo-and granulocytopoiesis as well as its immunostimulating, antineurodegenerative and other properties were demonstrated in previous studies [21]. Recent findings [22] demonstrated a two to threefold increase of CFC numbers in methylcellulose cultures of rat bone marrow obtained on Day 4 after PRP 10 lg administration. PRP addition to cultures of bone marrow obtained from control animals and from rats which had been administered PRP did not result in any additional increase of colonies.…”

Hypothalamic Proline Rich Polypeptide Regulates Hematopoiesis

“…Recently we found that PRP-1 increased colony-forming cell (CFC) proliferation in rat BM cells in vivo, whereas the related peptide [arg 8 ] vasopressin did not reveal CFC proliferation. Moreover, PRP-1 increased the appearance of CD14 positive cells upon 3-4 day incubation with both adult and fetal BM stromal cells [15]. These results suggest a previously indescribed role for the hypothalamic peptide within neurosecretory hypothalamus-bone marrow humoral axis, since PRP enhances BM colony forming cell proliferation and stromal cell differentiation.…”

“…The related peptide [arg 8 ] vasopressin did not reveal CFC proliferation. Interesting, that PRP-1 increased the appearance of CD14 positive cells upon 3-4 day incubation with both adult and fetal human BM stromal cells [15]. One possible mechanism of such action would be influence of PRP-1 on BM cells apoptosis.…”

Epigenetic control of cancer by neuropeptides

“…PRP-1 is derived from its precursor, neurophysin-vasopressin-associated glycoprotein precursor (20). In addition, large quantities of PRP-1 were detected in bone marrow granulocytes (21). The antimicrobial, antitumorigenic and antineurodegenerative properties for this immunomodulatory cytokine were previously reported (22) and the quantification of hypothalamic PRP-1 in the blood was recently documented (23).…”