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Cellular basis of urothelial squamous metaplasia: roles of lineage heterogeneity and cell replacement.

Liang FX, Bosland MC, Huang H, Romih R, Baptiste S, Deng FM, Wu XR, Shapiro E, Sun TT - J. Cell Biol. (2005)

Bottom Line: Although the epithelial lining of much of the mammalian urinary tract is known simply as the urothelium, this epithelium can be divided into at least three lineages of renal pelvis/ureter, bladder/trigone, and proximal urethra based on their embryonic origin, uroplakin content, keratin expression pattern, in vitro growth potential, and propensity to keratinize during vitamin A deficiency.During vitamin A deficiency, mouse urothelium form multiple keratinized foci in proximal urethra probably originating from scattered K14-positive basal cells, and the keratinized epithelium expands horizontally to replace the surrounding normal urothelium.These data suggest that the urothelium consists of multiple cell lineages, that trigone urothelium is closely related to the urothelium covering the rest of the bladder, and that lineage heterogeneity coupled with cell migration/replacement form the cellular basis for urothelial squamous metaplasia.

View Article: PubMed Central - PubMed

Affiliation: Epithelial Biology Unit, The Ronald O. Perelman Department of Dermatology.

ABSTRACT
Although the epithelial lining of much of the mammalian urinary tract is known simply as the urothelium, this epithelium can be divided into at least three lineages of renal pelvis/ureter, bladder/trigone, and proximal urethra based on their embryonic origin, uroplakin content, keratin expression pattern, in vitro growth potential, and propensity to keratinize during vitamin A deficiency. Moreover, these cells remain phenotypically distinct even after they have been serially passaged under identical culture conditions, thus ruling out local mesenchymal influence as the sole cause of their in vivo differences. During vitamin A deficiency, mouse urothelium form multiple keratinized foci in proximal urethra probably originating from scattered K14-positive basal cells, and the keratinized epithelium expands horizontally to replace the surrounding normal urothelium. These data suggest that the urothelium consists of multiple cell lineages, that trigone urothelium is closely related to the urothelium covering the rest of the bladder, and that lineage heterogeneity coupled with cell migration/replacement form the cellular basis for urothelial squamous metaplasia.

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Expression of UPs and keratins in the urothelia of the mouse urinary tract. Paraffin sections of mouse skin (SK; a) and vaginal epithelium (V; b), bladder dome (BD; d–g), proximal urethra (PU; h–m for female and n and o for male), and spongy urethra (SU; p and q) were stained immunohistochemically using various antibodies to detect UP IIIa and keratins K1, K10, and K14 as indicated. (c) SDS-PAGE and immunoblot analyses of the total proteins of mouse skin (lane 1) and proximal urethral urothelium (lane 2) by silver nitrate staining (top) and immunoblotting using anti-K10 antibody (middle) and anti-K19 antibody (bottom). Note that the bladder dome urothelium was UP IIIa positive and K1/K10 negative and, in contrast, that the urothelium of the proximal urethra was UP positive in its superficial cell layer, K14 positive in some of its basal cells, and K1/K10 positive in its basal and intermediate cells. The boxed area in panel p is shown at a higher magnification in panel q. Ep, epidermis; H, hair follicle; L, lumen; B, bladder; S, skin. Bars (a, b, j, k, and q), 100 μm; (d–i and l–o) 200 μm; (p) 400 μm.
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fig4: Expression of UPs and keratins in the urothelia of the mouse urinary tract. Paraffin sections of mouse skin (SK; a) and vaginal epithelium (V; b), bladder dome (BD; d–g), proximal urethra (PU; h–m for female and n and o for male), and spongy urethra (SU; p and q) were stained immunohistochemically using various antibodies to detect UP IIIa and keratins K1, K10, and K14 as indicated. (c) SDS-PAGE and immunoblot analyses of the total proteins of mouse skin (lane 1) and proximal urethral urothelium (lane 2) by silver nitrate staining (top) and immunoblotting using anti-K10 antibody (middle) and anti-K19 antibody (bottom). Note that the bladder dome urothelium was UP IIIa positive and K1/K10 negative and, in contrast, that the urothelium of the proximal urethra was UP positive in its superficial cell layer, K14 positive in some of its basal cells, and K1/K10 positive in its basal and intermediate cells. The boxed area in panel p is shown at a higher magnification in panel q. Ep, epidermis; H, hair follicle; L, lumen; B, bladder; S, skin. Bars (a, b, j, k, and q), 100 μm; (d–i and l–o) 200 μm; (p) 400 μm.

Mentions: To better understand the cellular basis of urothelial heterogeneity, we stained sections of various zones of the normal female mouse urinary tract using antibodies to UPs and various keratins (Fig. 4). Control experiments showed that, as expected, the anti-K14 and -K1 antibodies stained mouse epidermis and vaginal epithelium mainly basally and suprabasally, respectively (Fig. 4, a and b), and that the anti-K10 antibody recognized a single 56.5-kD (K10) keratin in the total protein extract of the mouse skin epidermis (Fig. 4 c, lane 1) and proximal urethra (Fig. 4 c, lane 2), thus clearly establishing the specificities of the antibodies. Consistent with our previous results (Lin et al., 1994; Zhang et al., 1999), all suprabasal cell layers of the bladder dome urothelium expressed UPIIIa (Fig. 4 d) with no detectable K14 (a basal keratinocyte marker; Fig. 4 e) or K1 and K10 (keratinization markers; Fig. 4, f and g; Woodcock-Mitchell et al., 1982; Sun et al., 1984). The urothelium of the proximal urethra was also UP positive, although the staining was more limited to the superficial cell layer (Fig. 4 h). Some of its basal cells that were scattered expressed K14 (Fig. 4, i–k), and, unexpectedly, most of its basal and intermediate cells were K1 and K10 positive (Fig. 4, l and m). In the male mouse, the prostatic urethral epithelium exhibited UP/keratin patterns (Fig. 4, n and o) similar to those of the female proximal urethra. As expected, the epithelial lining of the spongy (of males) and distal urethra (of females) did not express UP but rather expressed K1/K10 suprabasally (Fig. 4, p and q), which is consistent with their close relation to the ectoderm-derived epidermis. Similar results were obtained with bovine urothelia.


Cellular basis of urothelial squamous metaplasia: roles of lineage heterogeneity and cell replacement.

Liang FX, Bosland MC, Huang H, Romih R, Baptiste S, Deng FM, Wu XR, Shapiro E, Sun TT - J. Cell Biol. (2005)

Expression of UPs and keratins in the urothelia of the mouse urinary tract. Paraffin sections of mouse skin (SK; a) and vaginal epithelium (V; b), bladder dome (BD; d–g), proximal urethra (PU; h–m for female and n and o for male), and spongy urethra (SU; p and q) were stained immunohistochemically using various antibodies to detect UP IIIa and keratins K1, K10, and K14 as indicated. (c) SDS-PAGE and immunoblot analyses of the total proteins of mouse skin (lane 1) and proximal urethral urothelium (lane 2) by silver nitrate staining (top) and immunoblotting using anti-K10 antibody (middle) and anti-K19 antibody (bottom). Note that the bladder dome urothelium was UP IIIa positive and K1/K10 negative and, in contrast, that the urothelium of the proximal urethra was UP positive in its superficial cell layer, K14 positive in some of its basal cells, and K1/K10 positive in its basal and intermediate cells. The boxed area in panel p is shown at a higher magnification in panel q. Ep, epidermis; H, hair follicle; L, lumen; B, bladder; S, skin. Bars (a, b, j, k, and q), 100 μm; (d–i and l–o) 200 μm; (p) 400 μm.
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fig4: Expression of UPs and keratins in the urothelia of the mouse urinary tract. Paraffin sections of mouse skin (SK; a) and vaginal epithelium (V; b), bladder dome (BD; d–g), proximal urethra (PU; h–m for female and n and o for male), and spongy urethra (SU; p and q) were stained immunohistochemically using various antibodies to detect UP IIIa and keratins K1, K10, and K14 as indicated. (c) SDS-PAGE and immunoblot analyses of the total proteins of mouse skin (lane 1) and proximal urethral urothelium (lane 2) by silver nitrate staining (top) and immunoblotting using anti-K10 antibody (middle) and anti-K19 antibody (bottom). Note that the bladder dome urothelium was UP IIIa positive and K1/K10 negative and, in contrast, that the urothelium of the proximal urethra was UP positive in its superficial cell layer, K14 positive in some of its basal cells, and K1/K10 positive in its basal and intermediate cells. The boxed area in panel p is shown at a higher magnification in panel q. Ep, epidermis; H, hair follicle; L, lumen; B, bladder; S, skin. Bars (a, b, j, k, and q), 100 μm; (d–i and l–o) 200 μm; (p) 400 μm.
Mentions: To better understand the cellular basis of urothelial heterogeneity, we stained sections of various zones of the normal female mouse urinary tract using antibodies to UPs and various keratins (Fig. 4). Control experiments showed that, as expected, the anti-K14 and -K1 antibodies stained mouse epidermis and vaginal epithelium mainly basally and suprabasally, respectively (Fig. 4, a and b), and that the anti-K10 antibody recognized a single 56.5-kD (K10) keratin in the total protein extract of the mouse skin epidermis (Fig. 4 c, lane 1) and proximal urethra (Fig. 4 c, lane 2), thus clearly establishing the specificities of the antibodies. Consistent with our previous results (Lin et al., 1994; Zhang et al., 1999), all suprabasal cell layers of the bladder dome urothelium expressed UPIIIa (Fig. 4 d) with no detectable K14 (a basal keratinocyte marker; Fig. 4 e) or K1 and K10 (keratinization markers; Fig. 4, f and g; Woodcock-Mitchell et al., 1982; Sun et al., 1984). The urothelium of the proximal urethra was also UP positive, although the staining was more limited to the superficial cell layer (Fig. 4 h). Some of its basal cells that were scattered expressed K14 (Fig. 4, i–k), and, unexpectedly, most of its basal and intermediate cells were K1 and K10 positive (Fig. 4, l and m). In the male mouse, the prostatic urethral epithelium exhibited UP/keratin patterns (Fig. 4, n and o) similar to those of the female proximal urethra. As expected, the epithelial lining of the spongy (of males) and distal urethra (of females) did not express UP but rather expressed K1/K10 suprabasally (Fig. 4, p and q), which is consistent with their close relation to the ectoderm-derived epidermis. Similar results were obtained with bovine urothelia.

Bottom Line: Although the epithelial lining of much of the mammalian urinary tract is known simply as the urothelium, this epithelium can be divided into at least three lineages of renal pelvis/ureter, bladder/trigone, and proximal urethra based on their embryonic origin, uroplakin content, keratin expression pattern, in vitro growth potential, and propensity to keratinize during vitamin A deficiency.During vitamin A deficiency, mouse urothelium form multiple keratinized foci in proximal urethra probably originating from scattered K14-positive basal cells, and the keratinized epithelium expands horizontally to replace the surrounding normal urothelium.These data suggest that the urothelium consists of multiple cell lineages, that trigone urothelium is closely related to the urothelium covering the rest of the bladder, and that lineage heterogeneity coupled with cell migration/replacement form the cellular basis for urothelial squamous metaplasia.

View Article: PubMed Central - PubMed

Affiliation: Epithelial Biology Unit, The Ronald O. Perelman Department of Dermatology.

ABSTRACT
Although the epithelial lining of much of the mammalian urinary tract is known simply as the urothelium, this epithelium can be divided into at least three lineages of renal pelvis/ureter, bladder/trigone, and proximal urethra based on their embryonic origin, uroplakin content, keratin expression pattern, in vitro growth potential, and propensity to keratinize during vitamin A deficiency. Moreover, these cells remain phenotypically distinct even after they have been serially passaged under identical culture conditions, thus ruling out local mesenchymal influence as the sole cause of their in vivo differences. During vitamin A deficiency, mouse urothelium form multiple keratinized foci in proximal urethra probably originating from scattered K14-positive basal cells, and the keratinized epithelium expands horizontally to replace the surrounding normal urothelium. These data suggest that the urothelium consists of multiple cell lineages, that trigone urothelium is closely related to the urothelium covering the rest of the bladder, and that lineage heterogeneity coupled with cell migration/replacement form the cellular basis for urothelial squamous metaplasia.

Show MeSH
Related in: MedlinePlus