Histatin-1 Expression in Human Lacrimal Epithelium

Shah, Dhara; Ali, Mohsin; Pasha, Zeeshan; Jaboori, Assraa Jassim; Jassim, Sarmad; Jain, Sandeep; Aakalu, Vinay K.

doi:10.1371/journal.pone.0148018

Cited by 16 publications

(22 citation statements)

References 33 publications

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“…Histatins were originally described as antibacterial histidine-rich peptides in saliva [15], but have since been noted for their anti-fungal and wound healing activities [7]. In addition, histatins appear to have a variety of anti-proteolytic abilities and have been found to inhibit matrix metalloproteinase (MMP) activity.…”

Section: Discussionmentioning

confidence: 99%

Effects of histatin-1 peptide on human corneal epithelial cells

et al. 2017

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PurposeOcular surface and corneal epithelial wounds are common and potentially debilitating problems. Ideal treatments for these injuries would promote epithelial healing without inflammation, infection and scarring. In addition the best treatments would be cost-efficient, effective, non-toxic and easily applied. Histatin-1 peptides have been shown to be safe and effective enhancers of epithelial wound healing in other model systems. We sought to determine whether histatin-1 peptides could enhance human corneal epithelial wound healing in vitro.MethodsHistatin-1 peptides were applied to human corneal epithelial cells and compared over useful dose ranges in scratch assays using time-lapse microscopy. In addition, path finding analysis, cell spreading assays, toxicity and proliferation assays were performed to further characterize the effects of histatin-1 peptide on human corneal limbal epithelial (HCLE).ResultsHistatin-1 enhanced human corneal epithelial wound healing in typical wound healing models. There was minimal toxicity and no significant enhancement of proliferation of corneal epithelium in response to histatin-1 application. Corneal epithelial spreading and pathfinding appeared to be enhanced by the application of histatin-1 peptides.ConclusionsHistatin -1 peptide may enhance migration of HCLE cells and wound healing in vitro. These peptides may have benefit in corneal epithelial wounds and need to be investigated further.

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Section: Discussionmentioning

confidence: 99%

Effects of histatin-1 peptide on human corneal epithelial cells

et al. 2017

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“…These proteins are synthesized and secreted by the serous acini of the parotid, submandibular, sublingual, and von Ebner glands (Ahmad, Piludu, Oppenheim, Helmerhorst, & Hand, 2004;Sabatini & Azen, 1989;Schenkels, Veerman, & Nieuw Amerongen, 1995;vanderSpek et al, 1989;Takano, Malamud, Bennick, Oppenheim, & Hand, 1993). Intriguingly, recent reports have detected the expression of these peptides in other tissues, for instance, histatin-1 in human lacrimal gland (Ali et al, 2017;Shah et al, 2016), melanoma cell lines, and metastatic lesions of patients diagnosed with melanoma (Yaguchi & Kawakami, 2012), and histatin-5 in human ocular surface (Steele, Jumblatt, Smith, & Pierce, 2002).…”

Section: The Histatinsmentioning

confidence: 99%

Histatins, wound healing, and cell migration

et al. 2018

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Wounds in the oral mucosa heal faster and more efficiently than those in the skin, although the mechanisms underlying these differences are not completely clear. In the last 10 years, a group of salivary peptides, the histatins, has gained attention on behalf of their ability to improve several phases of the wound-healing process. In addition to their roles as anti-microbial agents and in enamel maintenance, histatins elicit other biological effects, namely by promoting the migration of different cell types contained in the oral mucosa and in non-oral tissues. Histatins, and specifically histatin-1, promote cell adhesion and migration in oral keratinocytes, gingival and dermal fibroblasts, non-oral epithelial cells, and endothelial cells. This is particularly relevant, as histatin-1 promotes the re-epithelialization phase and the angiogenic responses by increasing epithelial and endothelial cell migration. Although the molecular mechanisms associated with histatin-dependent cell migration remain poorly understood, recent studies have pointed to the control of signaling endosomes and the balance of small GTPases. This review aimed to update the literature on the effects of histatins in cell migration, with a focus on wound healing. We will also discuss the consequences that this increasing field will have in disease and therapy design.

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“…In addition, we studied the localization of histatin-1, a protein previously thought to be primarily expressed in salivary tissues 39 . In a recent study, we demonstrated that histatin-1 is a useful marker for lacrimal epithelium 25 . We also attempted to correlate immuno-localization results to relevant patient characteristics.…”

Section: Discussionmentioning

confidence: 96%

“…Aquaporin-5 is a water channel protein also involved in tear generation process 24 . We recently demonstrated the utility of histatin-1 as a potential lacrimal epithelial marker, but a gold-standard lacrimal epithelial marker should be determined through the use of multiple studies and we utilize multiple markers to phenotype lacrimal epithelial cells 25 .…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Accessory Lacrimal Gland in Muller’s Muscle Conjunctival Resection Specimens for Precursor Cell Markers and Biological Markers of Dry Eye Disease

Ali

Shah

Pasha

et al. 2016

Current Eye Research

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Purpose The accessory lacrimal glands (ALG) are an understudied component of the tear functional unit, even though they are important in the development of dry eye syndrome (DES). To advance our understanding of aging changes, regenerative potential and histologic correlates to human characteristics, we investigated human ALG tissue from surgical samples to determine the presence or absence of progenitor cell markers and lacrimal epithelial markers and to correlate marker expression to relevant patient characteristics. Materials and Methods ALG tissues obtained from Muller’s Muscle Conjunctival Resection (MMCR) specimens were created using tissue microarrays (TMAs). Immunofluorescence staining of MMCR sections was performed using primary antibodies specific to cell protein markers. Cell marker localization in TMAs was then assessed by two blinded observers using a standardized scoring system. Patient characteristics including age, race, and status of ocular surface health were then compared against expression of stem cell markers. Results Human ALG expressed a number of epithelial markers, and in particular, histatin-1 was well correlated with the expression of epithelial markers and was present in most acini. In addition, we noted the presence of precursor cell markers nestin, ABCG2 and CD90 in ALG tissue. There was a decrease in precursor cell marker expression with increasing age. Finally, we noted that a negative association was present between histatin-1 expression and DES. Conclusions Thus, we report for the first time that human ALG tissues contain precursor marker positive cells and that this marker expression may decrease with increasing age. Moreover, histatin-1 expression may be decreased in DES. Future studies will be performed to use these cell markers to isolate and culture lacrimal epithelial cells from heterogeneous tissues, determine the relevance of histatin-1 expression to DES and isolate candidate precursor cells from ALG tissue.

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Histatin-1 Expression in Human Lacrimal Epithelium

Cited by 16 publications

References 33 publications

Effects of histatin-1 peptide on human corneal epithelial cells

Effects of histatin-1 peptide on human corneal epithelial cells

Histatins, wound healing, and cell migration

Evaluation of Accessory Lacrimal Gland in Muller’s Muscle Conjunctival Resection Specimens for Precursor Cell Markers and Biological Markers of Dry Eye Disease

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