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The role of p38b MAPK in age-related modulation of intestinal stem cell proliferation and differentiation in Drosophila.

Park JS, Kim YS, Yoo MA - Aging (Albany NY) (2009)

Bottom Line: In addition, this pathway is involved in age and oxidative stress-associated mis-differentiation of enterocytes and upregulation of Delta, a Notch receptor ligand.Furthermore, we also show that D-p38b acts downstream of PVF2/PVR signaling in these age-related changes.Taken together, our findings suggest that p38 MAPK plays a crucial role in the balance between ISC proliferation and proper differentiation in the adult Drosophila midgut.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, Pusan National University, Busan 609-735, Korea.

ABSTRACT
It is important to understand how age-related changes in intestinal stem cells (ISCs) may contribute to age-associated intestinal diseases, including cancer. Drosophila midgut is an excellent model system for the study of ISC proliferation and differentiation. Recently, age-related changes in the Drosophila midgut have been shown to include an increase in ISC proliferation and accumulation of mis-differentiated ISC daughter cells. Here, we show that the p38b MAPK pathway contributes to the age-related changes in ISC and progenitor cells in Drosophila. D-p38b MAPK is required for an age-related increase of ISC proliferation. In addition, this pathway is involved in age and oxidative stress-associated mis-differentiation of enterocytes and upregulation of Delta, a Notch receptor ligand. Furthermore, we also show that D-p38b acts downstream of PVF2/PVR signaling in these age-related changes. Taken together, our findings suggest that p38 MAPK plays a crucial role in the balance between ISC proliferation and proper differentiation in the adult Drosophila midgut.

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Increased expression of D-p38b in ISCs and EBs within aged gut. (A)                                        Increased expression of D-p38b-lacZ reporter construct in the adult                                        posterior midgut with age. The midguts of 5- and 30-day-old flies,                                        including those with two copies of the D-p38b-lacZ, were examined by                                        X-gal staining. Squared boxes are enlarged images. Arrow head indicates β-gal-positive                                        cells. Original magnification is 400x. (B) Increased expression of D-p38b-lacZ                                        reporter construct in the Delta-positive and neighboring cells in aged gut.                                        The midguts of 30-day-old flies were examined with anti-β-gal and                                        anti-Delta. Anti-β-gal, green; anti-Delta, red; DAPI, blue. Scale bar,                                        1 μM.
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Figure 1: Increased expression of D-p38b in ISCs and EBs within aged gut. (A) Increased expression of D-p38b-lacZ reporter construct in the adult posterior midgut with age. The midguts of 5- and 30-day-old flies, including those with two copies of the D-p38b-lacZ, were examined by X-gal staining. Squared boxes are enlarged images. Arrow head indicates β-gal-positive cells. Original magnification is 400x. (B) Increased expression of D-p38b-lacZ reporter construct in the Delta-positive and neighboring cells in aged gut. The midguts of 30-day-old flies were examined with anti-β-gal and anti-Delta. Anti-β-gal, green; anti-Delta, red; DAPI, blue. Scale bar, 1 μM.

Mentions: To determine the role of D-p38b MAPK in age-related changes in the adult Drosophila midgut, we first investigated D-p38b expression in the adult midgut using transgenic flies carrying a D-p38b-lacZ reporter construct [15]. Increased expression of the D-p38b-lacZ reporter construct in aged midgut was detected by X-gal staining (Figure 1A). In Figure 1B, we analyzed the expression pattern of D-p38b-lacZ in the aged guts using anti-β-gal antibody and anti-Delta antibody, a marker of ISC [4,5]. Interestingly, the expression pattern of D-p38b-lacZ in young and aged posterior midguts indicates that the expression of D-p38b-lacZ increases in ISCs and neighboring cells in the adult Drosophila midgut.


The role of p38b MAPK in age-related modulation of intestinal stem cell proliferation and differentiation in Drosophila.

Park JS, Kim YS, Yoo MA - Aging (Albany NY) (2009)

Increased expression of D-p38b in ISCs and EBs within aged gut. (A)                                        Increased expression of D-p38b-lacZ reporter construct in the adult                                        posterior midgut with age. The midguts of 5- and 30-day-old flies,                                        including those with two copies of the D-p38b-lacZ, were examined by                                        X-gal staining. Squared boxes are enlarged images. Arrow head indicates β-gal-positive                                        cells. Original magnification is 400x. (B) Increased expression of D-p38b-lacZ                                        reporter construct in the Delta-positive and neighboring cells in aged gut.                                        The midguts of 30-day-old flies were examined with anti-β-gal and                                        anti-Delta. Anti-β-gal, green; anti-Delta, red; DAPI, blue. Scale bar,                                        1 μM.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2806044&req=5

Figure 1: Increased expression of D-p38b in ISCs and EBs within aged gut. (A) Increased expression of D-p38b-lacZ reporter construct in the adult posterior midgut with age. The midguts of 5- and 30-day-old flies, including those with two copies of the D-p38b-lacZ, were examined by X-gal staining. Squared boxes are enlarged images. Arrow head indicates β-gal-positive cells. Original magnification is 400x. (B) Increased expression of D-p38b-lacZ reporter construct in the Delta-positive and neighboring cells in aged gut. The midguts of 30-day-old flies were examined with anti-β-gal and anti-Delta. Anti-β-gal, green; anti-Delta, red; DAPI, blue. Scale bar, 1 μM.
Mentions: To determine the role of D-p38b MAPK in age-related changes in the adult Drosophila midgut, we first investigated D-p38b expression in the adult midgut using transgenic flies carrying a D-p38b-lacZ reporter construct [15]. Increased expression of the D-p38b-lacZ reporter construct in aged midgut was detected by X-gal staining (Figure 1A). In Figure 1B, we analyzed the expression pattern of D-p38b-lacZ in the aged guts using anti-β-gal antibody and anti-Delta antibody, a marker of ISC [4,5]. Interestingly, the expression pattern of D-p38b-lacZ in young and aged posterior midguts indicates that the expression of D-p38b-lacZ increases in ISCs and neighboring cells in the adult Drosophila midgut.

Bottom Line: In addition, this pathway is involved in age and oxidative stress-associated mis-differentiation of enterocytes and upregulation of Delta, a Notch receptor ligand.Furthermore, we also show that D-p38b acts downstream of PVF2/PVR signaling in these age-related changes.Taken together, our findings suggest that p38 MAPK plays a crucial role in the balance between ISC proliferation and proper differentiation in the adult Drosophila midgut.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, Pusan National University, Busan 609-735, Korea.

ABSTRACT
It is important to understand how age-related changes in intestinal stem cells (ISCs) may contribute to age-associated intestinal diseases, including cancer. Drosophila midgut is an excellent model system for the study of ISC proliferation and differentiation. Recently, age-related changes in the Drosophila midgut have been shown to include an increase in ISC proliferation and accumulation of mis-differentiated ISC daughter cells. Here, we show that the p38b MAPK pathway contributes to the age-related changes in ISC and progenitor cells in Drosophila. D-p38b MAPK is required for an age-related increase of ISC proliferation. In addition, this pathway is involved in age and oxidative stress-associated mis-differentiation of enterocytes and upregulation of Delta, a Notch receptor ligand. Furthermore, we also show that D-p38b acts downstream of PVF2/PVR signaling in these age-related changes. Taken together, our findings suggest that p38 MAPK plays a crucial role in the balance between ISC proliferation and proper differentiation in the adult Drosophila midgut.

Show MeSH
Related in: MedlinePlus