Diacylglycerol Signaling

316 A.K. Verma
UVR-induced release of TNFa and inflammation (Wheeler et al. 2004). The dorsal
skin of UVR-exposed PKCe transgenic mice exhibited severely hyperplastic interfollicular
epidermis with alternating regions of ulceration associated with severe
scarring. The scar tissue also contained remarkable amounts of inflammatory infiltrate.
In addition, the skin histopathology exhibited a disorganization of the hair
follicle and hyperplasia of the bulb region. The PKCe transgenic-TNFa knockout
skin was intact and showed significant reduction in both the interfollicular and follicular
hyperplasia, relative to the PKCe transgenic mice (Wheeler et al. 2004).
15.2.3.1 PKCe-Induced Release of TNFa May Stimulate Proliferation
of Keratinocyte Stem Cells, SCC Precursor Cells
In adult skin, each hair follicle contains a reservoir of stem cells, which can be
mobilized to regenerate the new follicle with each hair cycle and to reepithelialize
epidermis during wound repair (Tumbar et al. 2004). Several lines of evidence suggest
that epithelial stem cells reside in the bulge (Tumbar et al. 2004; Kangsamaksin
et al. 2007; Chebotaev et al. 2007; Trempus et al. 2003; Faurschou et al. 2007).
Epidermal stem cells in the mouse hair follicle are known to be the precursor cells
for SCC in the mouse skin (Tumbar et al. 2004; Kangsamaksin et al. 2007;
Chebotaev et al. 2007; Trempus et al. 2003; Faurschou et al. 2007). Stem cells,
unlike transit amplifying cells, are slowly cycling, and thus seem probable target
cells. Moreover, stem cells may retain those mutations and pass them on to their
progeny (Tumbar et al. 2004).
Morris et al. (2000) demonstrated that label retaining cells (LRCs) retain
carcinogen-DNA adducts, another property characteristic of potential initiated
cells. Morris et al. (2000) also determined the contribution of follicular and interfollicular
stem cells to the induction of skin papillomas and carcinomas. Both follicular
and interfollicular stem cells contributed to the development of papillomas. However,
only follicular stem cells were linked to the development of carcinomas.
It has recently become possible to isolate living hair follicle stem and progenitor
cells from mouse skin because of the discovery of cell surface properties that facilitate
enrichment (Gerdes and Yuspa 2005; Lavker and Sun 2000; Liu et al. 2003).
The cell surface markers CD34, K15, and a6-integrin mark mouse hair follicle
bulge cells, which have attributes of stem cells, including quiescence and multipotency.
About 30% of bulge keratinocytes are putative stem cells; however, there is
no immunostaining for stem cells specifically. CD34 will mark all bulge keratinocytes.
a6-integrin will mark all basal keratinocytes in the hair follicle and interfollicular
epidermis. LRCs in the bulge region are putative SCs. SCC in PKCe
transgenic mice appears to develop and invade from the hair follicle (Jansen et al.
2001a). However, the mechanism by which hair follicle stem cells are activated and
induced to proliferate is unknown. This remains to be determined whether PKCemediated
UVR-induced release of TNFa promote the proliferation of hair follicle
putative stem cells.