Focus on Molecules: Lacritin

Ma, Peisong; Wang, Ningning; McKown, Robert L.; Raab, Ronald W.; Laurie, Gordon W.

doi:10.1016/j.exer.2007.01.025

Cited by 16 publications

(13 citation statements)

References 4 publications

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“…The internal Lacrt control was liberated from the ELP tag via thrombin cleavage. Similar to previous reports [23], Lacrt ran higher on SDS-PAGE than the expected M.W. of 12 kDa (Fig.…”

Section: Resultssupporting

confidence: 92%

“…Interestingly, Lacrt displays growth factor-like behavior; however, its specificity for target cells of the ocular surface system results from a unique ‘off-on’ switch controlled by heparanase deglycanation of the cell surface protein, syndecan-1 [20], which both exposes and generates a Lacrt binding site [21] as a prerequisite for mitogenic signaling. Confirmed by 2-D electrophoresis, mass spectrometry and surface-enhanced laser desorption/ionization studies, Lacrt [22] is down regulated in blepharitis (chronic inflammation of the eyelid) vs. normal tears [23], and most aqueous deficient dry eye [24]. Whether down regulation of Lacrt provokes disease is a key unresolved question, but its prosecretory and corneal mitogenic activity suggest it might have activity as a protein therapeutic for ocular surface diseases.…”

Section: Introductionmentioning

confidence: 99%

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A thermo-responsive protein treatment for dry eyes

Wang

Jashnani

Aluri

et al. 2015

Journal of Controlled Release

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Millions of Americans suffer from dry eye disease, and there are few effective therapies capable of treating these patients. A decade ago, an abundant protein component of human tears was discovered and named lacritin(Lacrt). Lacrt has prosecretory activity in the lacrimal gland and mitogenic activity at the corneal epithelium. Similar to other proteins placed on the ocular surface, the durability of its effect is limited by rapid tear turnover. Motivated by the rationale that a thermo-responsive coacervate containing Lacrt would have better retention upon administration, we have constructed and tested the activity of a thermo-responsive Lacrt fused to an Elastin-like polypeptide (ELP). Inspired from the human tropoelastin protein, ELP protein polymers reversibly phase separate into viscous coacervates above a tunable transition temperature. This fusion construct exhibited the prosecretory function of native Lacrt as illustrated by its ability to stimulate β-hexosaminidase secretion from primary rabbit lacrimal gland acinar cells. It also increased tear secretion from non-obese diabetic (NOD) mice, a model of autoimmune dacryoadenitis, when administered via intra-lacrimal injection. Lacrt ELP fusion proteins undergo temperature-mediated assembly to form a depot inside the lacrimal gland. We propose that these Lacrt ELP fusion proteins represent a potential therapy for dry eye disease and the strategy of ELP-mediated phase separation may have applicability to other diseases of the ocular surface.

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“…The internal Lacrt control was liberated from the ELP tag via thrombin cleavage. Similar to previous reports [23], Lacrt ran higher on SDS-PAGE than the expected M.W. of 12 kDa (Fig.…”

Section: Resultssupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

A thermo-responsive protein treatment for dry eyes

Wang

Jashnani

Aluri

et al. 2015

Journal of Controlled Release

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“…2C, red ovals). Truncations and the C terminus ("I3") of the lacritin-c splice variant (33,34) (Fig. 2C) with a sequence completely different from wild type were generated.…”

Section: Resultsmentioning

confidence: 99%

Lacritin Rescues Stressed Epithelia via Rapid Forkhead Box O3 (FOXO3)-associated Autophagy That Restores Metabolism

Wang

Zimmerman

Raab

et al. 2013

Journal of Biological Chemistry

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“…It has recently been suggested that the dermcidin gene is generated by gene duplication of the lacritin gene, which is located on chromosome 12, adjacent to the dermcidin gene [20]. Lacritin is specifically expressed in the lacrimal gland and is secreted into tears, where it might act as an eye-specific growth factor [21,22]. There are striking similarities between lacritin and dermcidin in that the two genes have a similar exonic structure and are both expressed in a secretory gland.…”

Section: Homologous Dermcidin Genes In Humans and Other Speciesmentioning

confidence: 99%

The Multiple Facets of Dermcidin in Cell Survival and Host Defense

Schittek¹

2012

J Innate Immun

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Eccrine sweat glands, which are distributed over the whole bodies of primates and humans, have long been regarded mainly to have a function in thermoregulation. However, the discovery of dermcidin-derived antimicrobial peptides in eccrine sweat demonstrated that sweat actively participates in the constitutive innate immune defense of human skin against infection. In the meantime, a number of studies proved the importance of dermcidin in skin host defense. Several reports also state that peptides processed from the dermcidin precursor protein exhibit a range of other biological functions in neuronal and cancer cells. This review summarizes the evidence gathered until now concerning the expression of dermcidin and the functional relevance of dermcidin-derived peptides.

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Focus on Molecules: Lacritin

Cited by 16 publications

References 4 publications

A thermo-responsive protein treatment for dry eyes

A thermo-responsive protein treatment for dry eyes

Lacritin Rescues Stressed Epithelia via Rapid Forkhead Box O3 (FOXO3)-associated Autophagy That Restores Metabolism

The Multiple Facets of Dermcidin in Cell Survival and Host Defense

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