Effects of all-trans retinoic acid on goat dermal papilla cells cultured in vitro

Background: All-trans retinoic acid (ATRA), a vitamin A-derived active metabolite, exerts important functions in hair biology. Previous studies indicated that excess ATRA hampered hair follicle morphogenesis and cyclic regeneration in adulthood, but other studies stated that ATRA promoted hair growth. Dermal papilla (DP), a cluster of specialized fibroblasts, plays pivotal roles in controlling development and regeneration of hair follicle. Several lines of evidence indicated that DP might be the target cells of ATRA in the hair follicle. To confirm this hypothesis, the present study was performed to explore the biological effects of ATRA on goat dermal papilla cells (DPCs) and clarify the roles of ATRA in hair biology. Results: Our experimental results indicated that key signaling transducers of ATRA were dynamically expressed in distinct stages of goat cashmere growth cycle, and high-dose ATRA treatment (10-5 M) significantly impaired the viability of goat DPCs and lowered the ratio of proliferating cells. Otherwise, goat DPCs were stimulated to enter apoptosis and their cell cycle progression was severely blocked by ATRA. Moreover, the expression of fibroblast growth factor 7 (Fgf7), one of the potent hair growth stimulators secreted by DPCs, was transcriptionally repressed following ATRA treatment. Conclusion: DPCs are the targets of ATRA in the hair follicle, and ATRA negatively regulates hair growth by the targeted suppression of cell viability and growth factor expression of goat DPCs. Through these observations, we offer a new mechanistic insight into the roles of ATRA in hair biology.

Regulation of Expression of Sprouty Isoforms by EGF, FGF7 or FGF10 in Fetal Mouse Submandibular Glands / Oral Science International

Branching morphogenesis of the fetal mouse submandibular gland (SMG) is regulated by signaling through the ErbB and FGF families of tyrosine kinase receptors, whose members activate the ERK-1/2 pathway. The four Sprouty (Spry) proteins are inhibitory modulators of ERK-1/2. There is little information on their expression during pre- and postnatal development of the SMG. Qualitative RT-PCR detected mRNAs for <i>Spry1, 2</i>, and <i>4</i> from embryonic day 13 (E13) through postnatal day 7 (P7), but only trace amounts of <i>Spry1</i> and <i>2</i> in adult SMGs. More sensitive quantitative RT-PCR revealed that transcripts for all four <i>Spry</i> isoforms are expressed, and each shows individual patterns of variation across fetal and early postnatal stages, and that there are very low levels of <i>Spry1</i> and <i>2</i>, but no <i>Spry3</i> and <i>4</i>, in adult glands. EGF, FGF7 and FGF10 upregulate expression of mRNA for <i>Spry1</i>, but only FGF7 upregulates <i>Spry2</i> mRNA. EGF strongly induces an activating phosphorylation of all four <i>Spry</i> isoforms, but both FGFs do so only minimally. Quantitative RT-PCR of samples collected by laser capture microdissection showed that transcripts for <i>Spry1</i> are confined to the epithelium of E13 SMG rudiments. The isoform-specific temporal variation in the patterns of expression of <i>Spry1, 2, 3</i> and <i>4</i> suggests a potentially important role for these negative modulators of growth-factor driven ras/ERK-1/2 signaling at stages when the SMG is most actively undergoing branching morphogenesis.

The expression of FGF-5 and FGF-7 in the cyclosporin a-induced gingival hyperplasia

Cyclosporin A-induced gingival hyperplasia is frequently found in the patients who have been received an immunosuppressant for the organ transplantation. However, its exact mechanism is still unknown. The expression of FGF-5 and FGF-7 were studied in cyclosporine A-induced gingival hyperplasia (CGH) and inflammatory gingival hyperplasia (IGH). Immunohistochemistry and in situ hybridization were used for localization of protein and mRNA. The expression of FGF-5 and FGF-7 was different from CGH and IGH. FGF-5 and FGF-7 was strongly expressed in fibroblast in CGH (P<0.005 and P<0.05, respectively). FGF-5 mRNA was localized in the middle portion of connective tissue. FGF-7 mRNA was also identified in fibroblasts and mast cells. In conclusion, FGF-5 and FGF-7 were produced excessively by fibroblasts in CGH. Considering their known functions, their expression in CGH is important for production of collagen and proliferation of fibroblasts.

The cDNA microarray study for the effect of FGF-5 administration on fibroblast