The matricellular protein periostin contributes to proper collagen function and is downregulated during skin aging.

BACKGROUND: Periostin is a secreted 90kDa matricellular protein, which is predominantly expressed in collagen-rich tissues. Collagen is the most abundant protein in mammals and has great tensile strength. Recent investigations have shown that periostin influences collagen fibrillogenesis and biomechanical properties of murine connective tissues. OBJECTIVE: We investigated the function of periostin concerning collagen homeostasis during intrinsic and extrinsic skin aging. For this purpose, human skin samples of young and old donors as well as samples of photoaged and sun-protected skin areas were analyzed for periostin expression. Using in vitro models, we determined the cell types responsible for periostin expression and performed functional analyses with periostin knockdown cells. METHODS: TaqMan Real-Time PCR, UV irradiation, knockdown experiments, immunostaining, electron microscopy, collagen degradation assay, collagen crosslink analysis. RESULTS: Periostin expression is highest in the papillary dermis and downregulated during skin aging. Fibroblasts and non-follicular skin derived precursors were identified as main source for periostin expression in human skin. Periostin knockdown in fibroblasts has no effect on collagen expression, but results in an increased fibril diameter and aberrant collagen structure. This leads to an increased susceptibility of collagen toward proteases, whereas recombinant periostin protects collagen fibrils from degradation. CONCLUSION: Our data show that periostin plays an important role for proper collagen assembly and homeostasis. During skin aging periostin expression decreases and contributes to the phenotype of aged skin.

Differential regulation of human and mouse telomerase reverse transcriptase (TERT) promoter activity during testis development.

In adult testis, telomerase activity is exclusively detectable during the early steps of spermatogenesis and is downregulated during differentiation to spermatozoa. Knowledge about telomerase activity during testis development from birth to adulthood is still scarce. Telomerase activity is regulated primarily via the transcriptional initiation of TERT expression which encodes its catalytic subunit. We used the hTERTp-lacZ transgenic mouse model that expresses the bacterial lacZ reporter gene under the control of an 8.0-kbp human TERT promoter fragment to analyze simultaneously endogenous mouse Tert gene expression as well as human TERT promoter activity during mouse testis development. We show that human TERT promoter activity increased during puberty and was highest in adult mouse testis whereas mouse Tert expression and telomerase activity were found to be high in testis from the earliest time point tested (6 days postpartum). Histological analysis revealed that beta-galactosidase expression, encoded by the lacZ reporter gene, is present in all seminiferous tubules in adult testis, but in a subset of tubules before puberty. We further analyzed the expression of SCF/ c-KIT, which was described to regulate spermatogonia proliferation and mouse Tert expression, in prepubertal and adult testis by immunohistochemistry. Whereas SCF and c-KIT were detectable in all seminiferous tubules, a spatial and preclusive expression pattern of human TERT promoter activity and activated c-KIT (p-c-KIT Tyr 567/569) was observed in prepubertal testes.

Telomeres and telomerase. A survey about methods and recent advances in cancer diagnostic and therapy.

Since the discovery that telomerase is repressed in most normal human somatic cells but strongly expressed in most human tumours, telomerase emerged as an attractive target for diagnostic, prognostic and therapeutic purposes to combat human cancer. In this review, a synopsis of methods detecting telomerase is presented evaluating their potential for diagnostic and prognostic use. Also, the most promising telomerase therapeutics are discussed in the light of recent advances in the field.