Characterization of Mouse Tissue Kallikrein 5

Rajapakse, S.; Ogiwara, Katsueki; Yamano, Noriko; Kimura, Atsushi; Hirata, Kyoji; Takahashi, Sumio; Takahashi, Takayuki

doi:10.2108/zsj.23.963

Cited by 2 publications

(1 citation statement)

References 19 publications

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“…KLK5 is a particularly interesting kallikrein. KLK5 is a (chymo)trypsin-like proteinase that mediates degradation of many extracellular matrix proteins including collagens I-IV, fibronectin, fibrinogen, and laminin (26,29). In addition, there is substantial evidence that KLK5 is a master regulator of other kallikrein inactive zymogens, acting to cleave many inactive pro-KLKs into their active extracellular matrix protein-degrading forms (2,6,27,34).…”

Section: Discussionmentioning

confidence: 99%

MiR-382 targeting of kallikrein 5 contributes to renal inner medullary interstitial fibrosis

Kriegel

Liu

Cohen

et al. 2012

Physiological Genomics

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Previously we have shown that microRNA miR-382 can facilitate loss of renal epithelial characteristics in cultured cells. This study examined the in vivo role of miR-382 in the development of renal interstitial fibrosis in a mouse model. Unilateral ureteral obstruction was used to induce renal interstitial fibrosis in mice. With 3 days of unilateral ureteral obstruction, expression of miR-382 in the obstructed kidney was increased severalfold compared with sham-operated controls. Intravenous delivery of locked nucleic acid-modified anti-miR-382 blocked the increase in miR-382 expression and significantly reduced inner medullary fibrosis. Expression of predicted miR-382 target kallikrein 5, a proteolytic enzyme capable of degrading several extracellular matrix proteins, was reduced with unilateral ureteral obstruction. Anti-miR-382 treatment prevented the reduction of kallikrein 5 in the inner medulla. Furthermore, the protective effect of the anti-miR-382 treatment against fibrosis was abolished by renal knockdown of kallikrein 5. Targeting of kallikrein 5 by miR-382 was confirmed by 3'-untranslated region luciferase assay. These data support a completely novel mechanism in which miR-382 targets kallikrein 5 and contributes to the development of renal inner medullary interstitial fibrosis. The study provided the first demonstration of an in vivo functional role of miR-382 in any species and any organ system.

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Section: Discussionmentioning

confidence: 99%

MiR-382 targeting of kallikrein 5 contributes to renal inner medullary interstitial fibrosis

Kriegel

Liu

Cohen

et al. 2012

Physiological Genomics

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Kallikreins on Steroids: Structure, Function, and Hormonal Regulation of Prostate-Specific Antigen and the Extended Kallikrein Locus

2010

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The 15 members of the kallikrein-related serine peptidase (KLK) family have diverse tissue-specific expression profiles and putative proteolytic functions. The kallikrein family is also emerging as a rich source of disease biomarkers with KLK3, commonly known as prostate-specific antigen, being the current serum biomarker for prostate cancer. The kallikrein locus is also notable because it is extraordinarily responsive to steroids and other hormones. Indeed, at least 14 functional hormone response elements have been identified in the kallikrein locus. A more comprehensive understanding of the transcriptional regulation of kallikreins may help the field make more informed hypotheses about the physiological functions of kallikreins and their effectiveness as biomarkers. In this review, we describe the organization of the kallikrein locus and the structure of kallikrein genes and proteins. We also focus on the transcriptional regulation of kallikreins by androgens, progestins, glucocorticoids, mineralocorticoids, estrogens, and other hormones in animal models and human prostate, breast, and reproductive tract tissues. The interaction of the androgen receptor with androgen response elements in the promoter and enhancer of KLK2 and KLK3 is also summarized in detail. There is evidence that all kallikreins are regulated by multiple nuclear receptors. Yet, apart from KLK2 and KLK3, it is not clear whether all kallikreins are direct transcriptional targets. Therefore, we argue that gaining more detailed information about the mechanisms that regulate kallikrein expression should be a priority of future studies and that the kallikrein locus will continue to be an important model in the era of genome-wide analyses.

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Characterization of Mouse Tissue Kallikrein 5

Cited by 2 publications

References 19 publications

MiR-382 targeting of kallikrein 5 contributes to renal inner medullary interstitial fibrosis

MiR-382 targeting of kallikrein 5 contributes to renal inner medullary interstitial fibrosis

Kallikreins on Steroids: Structure, Function, and Hormonal Regulation of Prostate-Specific Antigen and the Extended Kallikrein Locus

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