SAM pointed domain ETS factor (SPDEF) regulates terminal differentiation and maturation of intestinal goblet cells

Abstract

Background & Aims: SPDEF (also termed PDEF or PSE), is an ETS family transcription factor that regulates gene expression in the prostate and goblet cell hyperplasia in the lung. Spdef has been reported to be expressed in the intestine. In this paper, we identify an important role for Spdef in regulating intestinal epithelial cell homeostasis and differentiation.

Shp2/MAPK signaling controls goblet/paneth cell fate decisions in the intestine

“…Thus, in Mek1DD; Shp2 double mutant mice, goblet cells are rescued, and this appears to occur at the expense of paneth cells. This is reminiscent of the phenotype observed after overexpression of the Ets transcription factor Spdef; Spdef overexpression promoted goblet cell differentiation at the expense of paneth cells (22). In control mice, goblet and paneth cells produce the Ets transcription factor Spdef, as assessed by IHC (Fig.…”

“…1 A and B). The intervention was accompanied by a drop in mRNAs of Spdef, Muc2, and Gob5, which are typically expressed in goblet cells (21)(22)(23), as assessed by qRT-PCR ( Fig. 1 C and D).…”

“…In contrast, sustained activation of MAPK signaling by the Mek1DD allele has the converse effects. Paneth and goblet cells express overlapping sets of genes (22,39), and cells with initially intermediary phenotypes have indeed been described (35, 40). Paneth and goblet cells are thus closely related and originate from a common precursor (Fig.…”

Interleukin-13 (IL-13)/IL-13 Receptor α1 (IL-13Rα1) Signaling Regulates Intestinal Epithelial Cystic Fibrosis Transmembrane Conductance Regulator Channel-dependent Cl− Secretion

“…This finding is consistent with previous studies demonstrating that overexpression of IL-13 in the pulmonary compartment induces mucus hypersecretion (38 -40). Goblet cell differentiation in both the lung and intestine is thought to be regulated by the sterile ␣-motif-pointed domain-containing Ets-like factor (SPEDF) (41)(42)(43). Employing the lung-specific inducible IL-13 transgenic mice CCSP-rtTA/tet0-CMV-IL-13, investigators demonstrated that pulmonary IL-13-induced goblet cell hyperplasia is associated with induction of SPDEF expression (44).…”

Glucocorticoids alleviate intestinal ER stress by enhancing protein folding and degradation of misfolded proteins

“…Therefore, we examined the expression of mRNA for Muc2, Agr2, and the goblet cell transcription factor Spdef (Park et al, 2007;Gregorieff et al, 2009;Noah et al, 2010). Spdef and Muc2 were significantly decreased in Winnie Consistent with the AB staining, in the proximal and mid colon, the decrease in Muc2 precursor accumulation was less than in the distal colon.…”