Expression of Gross Cystic Disease Fluid Protein-15/Prolactininducible Protein in Rat Salivary Glands

Abstract

Gross cystic disease fluid protein-15 (GCDFP-15)/prolactin-inducible protein (PIP) is present at moderate levels in human submandibular and sublingual glands and is barely detectable in human parotid gland. The rodent homologue, PIP, has previously been identified in adult submandibular and lacrimal glands. Here we present the molecular characterization of rat PIP and show that this protein is a product of neonatal and adult rat submandibular, sublingual, and parotid glands. cDNA clones encoding rat PIP were isolated and sequenced. The deduced amino acid sequence of rat PIP shows 56% overall identity and 80% similarity with mouse PIP. By SDS-PAGE, secreted rat PIP has an apparent Mr of 17,000, with a minor proportion present as Mr 20-22,000 N-glycosylated forms. PIP was localized in rat salivary glands by immunogold silver staining. PIP was identified in acinar cells of developing and mature submandibular and parotid glands and at very low levels in sublingual gland serous demilunes. Typically, rat submandibular gland secretory proteins are produced by either acinar cell progenitors (Type III cells) or mature acinar cells. The expression pattern observed for PIP is similar to that previously reported for salivary peroxidase, an important component of nonimmune mucosal defense.

Proteomic Analysis of a 14.2 kDa Protein Isolated from Bali Cattle(Bos Sondaicus/Javanicus)Saliva Using Single Dimension Sodium Dodecyl Sulphate-Polyacrylamide Gel Electrophoresis and Matrix-Assisted Laser Desorption Ionization Time-of-Flight Tandem Mass Spectrometer

“…It is also known as gross cystic disease fluid protein-15 (GCDFP-15), which associates with secretory cell differentiation and is believed to originate from a limited set of tissues, including breast and salivary glands. PIP/GCDFP-15 has been reported to be expressed in rat salivary glands (Mirels et al, 1998). Expression of GCDFP-15/PIP homologue was also reported in mouse salivary gland, although its function is still doubtful (Lamy et al, 2010;Lamy and Mau, 2012), and the expression PIP homologue was also reported in Bos taurus cattle (Zimin et al, 2009).…”

“…The PIP is a prolactin and androgen regulated product of human breast tumor cell line T-47D (Mirels et al, 1998). It is also known as gross cystic disease fluid protein-15 (GCDFP-15), which associates with secretory cell differentiation and is believed to originate from a limited set of tissues, including breast and salivary glands.…”

Development of the rat sublingual gland: A light and electron microscopic immunocytochemical study

“…The remaining known sublingual secretory proteins are products of the serous demilunes. All known serous demilune-specific proteins-SMGB, PSP, and CSP-1 (as well as prolactin-inducible protein (PIP) (Mirels et al, 1998a) and peroxidase (Moriguchi et al, 1995;Redman et al, 1998), which were not examined in the current study)-are also products of the immature acinar cells of the developing parotid and submandibular glands (Strum, 1971;Yamashina and Barka, 1972;Redman and Field, 1993;Mirels et al, 1998a).…”

“…At early stages, type IIIP cells may contain a mixture of these heterogeneous secretory granules and typical type III cell granules containing only neonatal proteins, whereas later in development, type IIIP cells with both type IIIP and adult MGs are found. Some proteins characteristic of the neonatal submandibular proacinar cells (PIP and peroxidase) are also produced by the mature seromucous acinar cells (Strum and Karnovsky, 1970;Mirels et al, 1998a), whereas the major proacinar cell products (SMGB, SMGD, CSP-1, and PSP) are present only in some intercalated duct cells in the adult gland.…”

“…Although morphologically unique secretory granules are not a feature of immature parotid acinar cells, biochemical and immunocytochemical studies have demonstrated that, as in the submandibular gland, the complement of parotid acinar secretory proteins changes significantly during the third postnatal week. SMGB, PSP, CSP-1, PIP, and peroxidase are all products of the neonatal parotid acinar cells (Redman and Field, 1993;Sivakumar et al, 1998;Mirels et al, 1998a). By the fourth postnatal week, however, expression of both SMGB and CSP-1 is restricted to intercalated ducts, whereas adult acinar cells continue to produce PSP, PIP, and peroxidase, and initiate the synthesis of additional adult proteins (Lazowski et al, 1992;Charest et al, 1993;Sivakumar et al, 1998;Mirels et al, 1998a).…”