Oncomodulin and macrophages derived factors in pancreas injury and development paradigms

Abstract

Prior studies in the optic nerve injury paradigm showed conflicting data regarding production and significance of the Ca 2+ -binding protein oncomodulin (OCM). Some have shown its potent axon-regenerative or-growth attribute, where other showed little to no effect. We show here that pancreas inflammation lead to macrophages infiltration that produce OCM and inflamed tissues that express OCM receptors in vivo. In culture OCM has a cytostatic effect on embryonic pancreas explants. Secretory products of zymosanactivated macrophages are cytotoxic and factors derived from non-activated macrophages seem to promote pancreas development. It is our view that OCM is involved in protective injury response that allows through metabolism slowing sub-lethally injured cells to undergo recovery.

Oncomodulin: The Enigmatic Parvalbumin Protein

“…Benowitz and colleagues (Yin et al, 2006, 2009; Benowitz and Yin, 2008, 2010; Cui et al, 2009; Kurimoto et al, 2010, 2013; Benowitz and Popovich, 2011; de Lima et al, 2012; Siawaya et al, 2013; Marin et al, 2016) have extensively investigated the role of OCM in an inflammatory-mediated nerve regenerative model. The first report linking OCM to macrophage activity was using spontaneously immortalized NR8383 cells (Yin et al, 2006), a macrophage-like cell line isolated from normal rat alveolar lung tissue (Helmke et al, 1987).…”

“…However, OCM does not inherently confer enhanced regenerative properties across all cell types. In an experiment using 3-day pancreas explants from E13 rats, treatment with OCM or MCM suppresses gene expression of pancreas duodenum homeobox-1 (Pdx-1) and neurogenin3 (Ngn3), two genes with significant roles in the development of the pancreas (Siawaya et al, 2013). Further in vivo studies in the pancreas are warranted, but at the very least, OCM cannot be assumed to possess universal pro-regenerative capacities.…”

“…Later studies of the rat inner ear suggested that OCM was expressed mostly in cochlear outer hair cells (OHCs) and possibly within vestibular hair cells (Sakaguchi et al, 1998). More recently, OCM was validated in OHCs across mammalian species, in vestibular hair cells (Simmons et al, 2010; Tong et al, 2016; Hoffman et al, 2018), and in immune cells (Yin et al, 2006, 2009; Kurimoto et al, 2010; Siawaya et al, 2013). Indeed, the unique cell and tissue distribution (Tables s 1–3) displayed by OCM begs the question: what specialized role or function does OCM have that other mobile Ca 2+ buffers do not?…”

What Is Parvalbumin for?

“…OM is expressed mostly in cochlear outer hair cells and in vestibular hair cells [99][100][101]. OM was also found in immune cells [102][103][104].…”