Thyroxine treatments do not correct inner ear defects in tmprss1 mutant mice

Hanifa, Syazana; Scott, Hamish S.; Crewther, Pauline E.; Guipponi, Michel; Tan, Justin

doi:10.1097/wnr.0b013e32833dbd2d

Cited by 9 publications

(3 citation statements)

References 19 publications

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“…Hepsin deficiency, however, has been linked to aberrant tectorial membrane development and decreased myelination of the auditory nerve. These defects appear to be secondary to either low circulating levels of thyroid hormone or low responsiveness of inner ear tissues to thyroid hormone, but how hepsin would control thyroid hormone action is not evident and as yet unstudied (Guipponi et al 2007, 2008; Hanifa et al 2010). …”

Section: Cellular and Developmental Functions Of Membrane-anchored Sementioning

confidence: 99%

Membrane-Anchored Serine Proteases in Vertebrate Cell and Developmental Biology

Szabo¹,

Bugge

2011

Annu. Rev. Cell Dev. Biol.

115

133

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Analysis of vertebrate genome sequences at the turn of the millennium revealed that a vastly larger repertoire of enzymes execute proteolytic cleavage reactions within the pericellular and extracellular environments than was anticipated from biochemical and molecular analysis. Most unexpected was the unveiling of an entire new family of structurally unique multidomain serine proteases that are anchored directly to the plasma membrane. Unlike secreted serine proteases, which function primarily in tissue repair, immunity, and nutrient uptake, these membrane-anchored serine proteases regulate fundamental cellular and developmental processes, including tissue morphogenesis, epithelial barrier function, ion and water transport, cellular iron export, and fertilization. Here the cellular and developmental biology of this fascinating new group of proteases is reviewed. Particularly highlighted is how the study of membrane-anchored serine proteases has expanded our knowledge of the range of physiological processes that require regulated proteolysis at the cell surface.

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Section: Cellular and Developmental Functions Of Membrane-anchored Sementioning

confidence: 99%

Membrane-Anchored Serine Proteases in Vertebrate Cell and Developmental Biology

Szabo¹,

Bugge

2011

Annu. Rev. Cell Dev. Biol.

115

133

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“…The significance of the reduced thyroid hormone level in hepsin deficiency‐associated hearing loss was examined. Thyroxine treatment, before and after birth, failed to rescue the hearing loss in hepsin KO mice [100]. Additionally, no differences in serum thyroxine levels were found between WT and Hlb320 mice [79], making it unlikely that the hearing loss caused by hepsin deficiency is secondary to reduced thyroid hormone production.…”

Section: Hepsin Functions In Individual Tissuesmentioning

confidence: 99%

Hepsin: a multifunctional transmembrane serine protease in pathobiology

Wang

Sun

et al. 2020

The FEBS Journal

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Cell membrane-bound serine proteases are important in the maintenance of physiological homeostasis. Hepsin is a type II transmembrane serine protease highly expressed in the liver. Recent studies indicate that hepsin activates prohepatocyte growth factor in the liver to enhance Met signaling, thereby regulating glucose, lipid, and protein metabolism. In addition, hepsin functions in nonhepatic tissues, including the adipose tissue, kidney, and inner ear, to regulate adipocyte differentiation, urinary protein processing, and auditory function, respectively. In mouse models, hepsin deficiency lowers blood glucose, lipid, and protein levels, impairs uromodulin assembly in renal epithelial cells, and causes hearing loss. Elevated hepsin expression has also been found in many cancers. As a type II transmembrane protease, cell surface expression and zymogen activation are essential for hepsin activity. In this review, we discuss the current knowledge regarding hepsin biosynthesis, activation, and functions in pathobiology.

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“…Hepsin is also expressed in kidney, pancreas, stomach, prostate and thyroid (Tsuji et al, 1991a,b). Studies of knockout mouse models of hepsin have demonstrated that this protease plays an important role in cochlear development, is involved in regulating levels of the thyroid secreted hormone, thyroxine, and is responsible for pro-HGF activation in the liver (Guipponi et al, 2007; Hanifa et al, 2010; Hsu et al, 2012). …”

Section: Hepsinmentioning

confidence: 99%

Type II transmembrane serine proteases as potential targets for cancer therapy

Murray

Varela

List

2016

Biological Chemistry

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Carcinogenesis is accompanied by increased protein and activity levels of extracellular cell-surface proteases that are capable of modifying the tumor micro-environment by directly cleaving the extracellular matrix, as well as activating growth factors and proinflammatory mediators involved in proliferation and invasion of cancer cells, and recruitment of inflammatory cells. These complex processes ultimately potentiate neoplastic progression leading to local tumor cell invasion, entry into the vasculature, and metastasis to distal sites. Several members of the type II transmembrane serine protease (TTSP) family have been shown to play critical roles in cancer progression. In this review the knowledge collected over the past two decades about the molecular mechanisms underlying the pro-cancerous properties of selected TTSPs will be summarized. Furthermore, we will discuss how these insights may facilitate the translation into clinical settings in the future by specifically targeting TTSPs as part of novel cancer treatment regimens.

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Thyroxine treatments do not correct inner ear defects in tmprss1 mutant mice

Cited by 9 publications

References 19 publications

Membrane-Anchored Serine Proteases in Vertebrate Cell and Developmental Biology

Membrane-Anchored Serine Proteases in Vertebrate Cell and Developmental Biology

Hepsin: a multifunctional transmembrane serine protease in pathobiology

Type II transmembrane serine proteases as potential targets for cancer therapy

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