scholarly journals Loss of NHE8 expression impairs ocular surface function in mice

2015 ◽  
Vol 308 (1) ◽  
pp. C79-C87 ◽  
Author(s):  
Hua Xu ◽  
Yang Zhao ◽  
Jing Li ◽  
Mingwu Wang ◽  
Fangru Lian ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Ocular Surface ◽  
Gastric Gland ◽  
Physiological Role ◽  
Sodium Absorption ◽  
Marker Genes ◽  
Tear Production ◽  
Sodium Hydrogen Exchanger ◽  
Human And Mouse

Sodium/hydrogen exchanger (NHE) 8 is expressed at the apical membrane of the epithelial cells and plays important roles in neutral sodium absorption in the gastrointestinal tract and the kidney. It also has an important role in epithelial mucosal protection in the gastric gland and the intestine. Although NHE8 has broad tissue distribution, the precise location and the physiological role of NHE8 in the eye remain unknown. In the present study, we successfully detected the expression of NHE8 in the ocular surface by PCR and Western blot in human and mouse eyes. Immunohistochemistry staining located NHE8 protein at the plasma membrane of the epithelial cells in the conjunctiva, the cornea, and the lacrimal gland both in human and mouse. We also detected the expression of downregulated-in-adenoma (DRA, a Cl−/HCO3− transporter) in the ocular surface epithelial cells. Using NHE8−/− mouse model, we found that loss of NHE8 function resulted in reduced tear production and increased corneal staining. These NHE8−/− mice also showed increased expression of TNF-α and matrix metalloproteinase 9 (MMP9) genes. The expression of epithelial keratinization marker genes, small proline-rich protein 2h (Sprr2h) and transglutaminase 1 (Tgm1), were also increased in NHE8−/− eyes. Furthermore, DRA expression in NHE8−/− mice was reduced in the conjunctiva, the cornea, and the lacrimal glands in association with a reduction in conjunctival mucosal pH. Altered ocular surface function and reduced epithelial DRA expression in NHE8−/− mice suggest that the role of NHE8 in ocular surface tissue involve in tear production and ocular epithelial protection. This study reveals a potential novel mechanism of dry eye condition involving abnormal NHE8 function.

scholarly journals Impaired mucin synthesis and bicarbonate secretion in the colon of NHE8 knockout mice

2012 ◽  
Vol 303 (3) ◽  
pp. G335-G343 ◽  
Author(s):  
Hua Xu ◽  
Bo Zhang ◽  
Jing Li ◽  
Chunhui Wang ◽  
Huacong Chen ◽  
...  
Keyword(s):  
Embryonic Stem ◽  
Physiological Role ◽  
Normal Serum ◽  
Sodium Absorption ◽  
Bicarbonate Secretion ◽  
Embryonic And Fetal Development ◽  
Sodium Hydrogen Exchanger ◽  
Important Player ◽  
Normal Serum Sodium

Sodium/hydrogen exchanger 8 (NHE8), the newest member of the SLC9 family, is expressed at the apical membrane of the epithelial cells in the intestine and the kidney. Although NHE8 has been shown to be an important player for intestinal sodium absorption early in development, its physiological role in the intestine remains unclear. Here, we successfully created a NHE8 knockout (NHE8−/−) mouse model to study the function of this transporter in the intestinal tract. Embryonic stem cells containing interrupted NHE8 gene were injected into mouse blastocyst to produce NHE8+/− chimeras. NHE8−/− mice showed no lethality during embryonic and fetal development. These mice had normal serum sodium levels and no signs of diarrhea. Apically expressed NHE2 and NHE3 were increased in the small intestine of the NHE8−/− mice in compensation. The number of goblet cells and mucin (MUC)-positive cells in the colon was reduced in NHE8−/− mice along with mucosal pH, MUC2 expression as well as downregulated in adenoma (DRA) expression. Therefore, the role of NHE8 in the intestine involves both sodium absorption and bicarbonate secretion.

scholarly journals TACSTD2 upregulation is an early reaction to lung infection

2021 ◽  
Author(s):  
Sara Lenart ◽  
Peter Lenart ◽  
Hana Kotasova ◽  
Vendula Pelkova ◽  
Veronika Sedlakova ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Physiological Role ◽  
Lung Epithelial Cells ◽  
Antibody Drug Conjugate ◽  
Epithelial Barrier Function ◽  
Transcriptomic Data ◽  
Transmembrane Glycoprotein ◽  
Lung Epithelial ◽  
Evolutionarily Conserved

TACSTD2 encodes a transmembrane glycoprotein Trop2 commonly overexpressed in carcinomas. While the Trop2 protein was discovered already in 1981 and first antibody-drug conjugate targeting Trop2 were recently approved cancer therapy, the physiological role of Trop2 is still not fully understood. In this article, we show that TACSTD2/Trop2 expression is evolutionarily conserved in lungs of various vertebrates. By analysis of publicly available transcriptomic data we demonstrate that TACSTD2 level consistently increases in lungs infected with miscellaneous pathogens. Single cell and subpopulation based transcriptomic data revealed that the major source of TACSTD2 transcript are lung epithelial cells and their progenitors and that TACSTD2 is induced directly in lung epithelial cells following infection. This increase may represent a mechanism to maintain/restore epithelial barrier function and contribute to regeneration process in infected/damaged lungs.

scholarly journals Glycodelin mRNA is expressed in the genital tract of male and female rats (Rattus norvegicus)

1999 ◽  
Vol 23 (1) ◽  
pp. 57-66 ◽  
Author(s):  
C Keil ◽  
B Husen ◽  
J Giebel ◽  
G Rune ◽  
R Walther
Keyword(s):  
Epithelial Cells ◽  
Reproductive Tract ◽  
In Situ Hybridisation ◽  
Physiological Role ◽  
Reproductive Organs ◽  
Female Rats ◽  
Male And Female Rats ◽  
First Time

In the present study we demonstrate for the first time the expression of glycodelin mRNA in the female and male genital tracts of rats using non-radioactive in situ hybridisation. Glycodelin fragment 1 (+41 to +141) shares 100% homology with the human gene sequence. In the ovary, glycodelin mRNA was restricted to granulosa cells. In the uterus, glycodelin mRNA was expressed in all epithelial cells of the endometrium. In the male reproductive tract, glycodelin mRNA was distributed in all epithelial cells of the epididymis, the prostate and the seminal vesicle. However, in the testis, glycodelin mRNA was predominantly found in spermatogonia and in spermatocytes of the seminiferous epithelium. The expression in several reproductive organs of rats offers an excellent tool to study further the physiological role of glycodelin, which is so far thought to act as an immunosuppressive factor.

A potential role for tissue kallikrein-related peptidases in human cervico-vaginal physiology

2008 ◽  
Vol 389 (6) ◽  
Author(s):  
Julie L.V. Shaw ◽  
Eleftherios P. Diamandis
Keyword(s):  
Epithelial Cells ◽  
Serine Proteases ◽  
Physiological Role ◽  
Matrix Proteins ◽  
Fetal Membrane ◽  
Vaginal Fluid ◽  
Tissue Kallikrein ◽  
Vaginal Epithelial Cells ◽  
Skin Physiology

AbstractHuman tissue kallikrein-related peptidases (KLK) are a family of 15 genes located on chromosome 19q13.4 that encode secreted serine proteases with trypsin- and/or chymotrypsin-like activity. Relatively large levels of many KLKs are present in human cervico-vaginal fluid (CVF) and in the supernatant of cultured human vaginal epithelial cells. Many KLKs are also hormonally regulated in vaginal epithelial cells, particularly by glucocorticoids and estrogens. The physiological role of KLK in the vagina is currently unknown; however, analysis of the CVF proteome has revealed clues for potential KLK functions in this environment. Here, we detail potential roles for KLKs in cervico-vaginal physiology. First, we suggest that KLKs play a role in the vagina similar to their role in skin physiology: (1) in the desquamation of vaginal epithelial cells, similar to their activity in the desquamation of skin corneocytes; and (2) in their ability to activate antimicrobial proteins in CVF as they do in sweat. Consequently, we hypothesize that dysregulated KLK expression in the vagina could lead to the development of pathological conditions such as desquamative inflammatory vaginitis. Second, we propose that KLKs may play a role in premature rupture of membranes and pre-term birth through their cleavage of fetal membrane extracellular matrix proteins.

Toll-Like Receptors in InflammAging at Ocular Surface.

2021 ◽  
Author(s):  
Antonio Zazzo ◽  
Maria Piano ◽  
Alessandra Micera ◽  
Tommaso Mori ◽  
Marco Coassin
Keyword(s):  
Ocular Surface ◽  
Physiological Role ◽  
Goblet Cells ◽  
Epifluorescence Microscopy ◽  
Toll Like Receptors ◽  
Schirmer Test ◽  
Age Related ◽  
Healthy Control ◽  
Homeostatic Mechanisms

Abstract Purpose: To evaluate changes in Toll Like Receptors expression at the ocular surface of healthy control volunteers within age. Methods: 51 volunteers were enrolled in a pilot observational study. Clinical (OSDI questionnaire, Schirmer test and BUT) and Biomolecular (ICAM1, Goblet cells) biomarkers were assessed in all subjects. Temporal Conjunctival imprints were used for molecular analysis while nasal ones were harvested for epifluorescence microscopy. Results: Within the age in our sample OSDI score increases, T-BUT values decrease, and goblet cells showed a decreasing trend. Relative real time PCR detected up-regulation of TLR2 and down-regulation of TLR7, TLR8 and MyD88 transcripts. Immunofluorescence data corroborated the PCR results reporting increased TLR2 and decreased TLR7 and TLR8 expression in elder population. A direct correlation was showed between increasing ICAM and increasing TLR2 changes with age. Conclusion: Changes in TLR expression are associated with aging, suggesting physiological role of TLRs in modulating innate and adaptive ocular surface immunity. TLRs age related changes may participate to the failure of ocular surface homeostatic mechanisms with inflammAging.

scholarly journals Role of amniotic membrane transplantation in ocular surface disorders

1970 ◽  
Vol 2 (2) ◽  
pp. 145-153 ◽  
Author(s):  
SK Arya ◽  
S Bhala ◽  
A Malik ◽  
S Sood
Keyword(s):  
Stem Cell ◽  
Epithelial Cells ◽  
Present Article ◽  
Dry Eye ◽  
Amniotic Membrane ◽  
Ocular Surface ◽  
Amniotic Membrane Transplantation ◽  
Surface Failure ◽  
Limbal Stem Cell

The advent of amniotic membrane (AM) and limbal stem cell grafts have transformed the treatment of diseases resulting in ocular surface failure. The current success may be attributed to cryopreservation of human AM, which retains its properties and renders the amniotic epithelial cells nonviable and thus nonimmunogenic. Its unique properties have prompted its application in a large number of ocular ailments. The present article reviews the properties of AM and its uses in ophthalmic practice. Keywords: amniotic membrane transplantation; ocular surface disorders; chemical injury; dry eye DOI: 10.3126/nepjoph.v2i2.3722 Nep J Oph 2010;2(2) 145-153

scholarly journals Novel Insight Into The Potential Role of AGPAT Gene Family in Triacylglycerols Synthesis in Buffalo

2021 ◽  
Author(s):  
Xiaoya Ma ◽  
Anqin Duan ◽  
Xingrong Lu ◽  
Md Mahmodul Hasan Sohel ◽  
Hamdy Abdel-Shafy ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Functional Characterization ◽  
Mammary Epithelial ◽  
Production Performance ◽  
Comparative Genomic ◽  
Marker Genes ◽  
Qrt Pcr ◽  
Rnai Technology

Abstract Background: Acylglycerophosphate acyltransferases (AGPATs) are enzymes known to act on the second acylation step in the Kennedy (de novo) pathway to catalyze the conversion of lysophosphatidic acid (LPA) to phosphatidic acid (PA). Although AGPATs have been extensively explored by evolution, expression, and functional studies, little is known about the functional characterization of how many members of the AGPAT family are involved in the triacylglycerols (TAG) synthesis. Therefore, the objective of this study was to characterize the potential functional roles of AGPAT family members in the TAG synthesis and growth of mammary epithelial cells using comparative genomic analysis and RNA interference (RNAi) technology.Results: In the present study, a total of 13 AGPAT genes in buffalo were identified using genome-wide analysis. Among them, 12 AGPAT gene pairs were orthologous between buffalo and cattle. The comparative transcriptomic analysis and real-time quantitative reverse transcription PCR (qRT-PCR) further showed that both AGPAT1 and AGPAT6 were highly expressed in milk samples of buffalo and cattle during lactation. Notably, knockdown of AGPAT1 or AGPAT6 significantly decreased the TAG content of buffalo mammary epithelial cells (BuMEC) and bovine mammary epithelial cells (BoMEC) through regulating the mRNA expression levels of several lipogenic genes. Furthermore, the knockdown of AGPAT1 or AGPAT6 inhibited proliferation and promoted apoptosis of BuMECs; the qRT-PCR analysis of marker genes associated with cell proliferation and apoptosis supported the same conclusions. Conclusions: These findings provide new insights about the members of AGPAT family on how they regulate the TAG synthesis and growth of mammary epithelial cells in buffalo. These findings will have important implications for understanding the role of AGPAT gene for buffalo milk production performance.

scholarly journals Knockout of the LRRC26 subunit reveals a primary role of LRRC26-containing BK channels in secretory epithelial cells

2017 ◽  
Vol 114 (18) ◽  
pp. E3739-E3747 ◽  
Author(s):  
Chengtao Yang ◽  
Vivian Gonzalez-Perez ◽  
Taro Mukaibo ◽  
James E. Melvin ◽  
Xiao-Ming Xia ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Physiological Role ◽  
Cell Types ◽  
Bk Channels ◽  
Specific Cell ◽  
Primary Role ◽  
Cellular Functions ◽  
Α Subunit ◽  
Voltage Dependent

Leucine-rich-repeat-containing protein 26 (LRRC26) is the regulatory γ1 subunit of Ca2+- and voltage-dependent BK-type K+ channels. BK channels that contain LRRC26 subunits are active near normal resting potentials even without Ca2+, suggesting they play unique physiological roles, likely limited to very specific cell types and cellular functions. By using Lrrc26 KO mice with a β-gal reporter, Lrrc26 promoter activity is found in secretory epithelial cells, especially acinar epithelial cells in lacrimal and salivary glands, and also goblet and Paneth cells in intestine and colon, although absent from neurons. We establish the presence of LRRC26 protein in eight secretory tissues or tissues with significant secretory epithelium and show that LRRC26 protein coassembles with the pore-forming BK α-subunit in at least three tissues: lacrimal gland, parotid gland, and colon. In lacrimal, parotid, and submandibular gland acinar cells, LRRC26 KO shifts BK gating to be like α-subunit-only BK channels. Finally, LRRC26 KO mimics the effect of SLO1/BK KO in reducing [K+] in saliva. LRRC26-containing BK channels are competent to contribute to resting K+ efflux at normal cell membrane potentials with resting cytosolic Ca2+ concentrations and likely play a critical physiological role in supporting normal secretory function in all secretory epithelial cells.

scholarly journals Current Understanding of Guanylin Peptides Actions

2013 ◽  
Vol 2013 ◽  
pp. 1-17 ◽  
Author(s):  
Aleksandra Sindic
Keyword(s):  
G Protein ◽  
Physiological Role ◽  
Intestinal Lumen ◽  
Sweat Glands ◽  
Sodium Absorption ◽  
G Protein Coupled Receptor ◽  
Guanylate Cyclase C ◽  
Water Secretion ◽  
G Protein Coupled

Guanylin peptides (GPs) family includes guanylin (GN), uroguanylin (UGN), lymphoguanylin, and recently discovered renoguanylin. This growing family is proposed to be intestinal natriuretic peptides. After ingestion of a salty meal, GN and UGN are secreted into the intestinal lumen, where they inhibit sodium absorption and induce anion and water secretion. At the same conditions, those hormones stimulate renal electrolyte excretion by inducing natriuresis, kaliuresis, and diuresis and therefore prevent hypernatremia and hypervolemia after salty meals. In the intestine, a well-known receptor for GPs is guanylate cyclase C (GC-C) whose activation increases intracellular concentration of cGMP. However, in the kidney of GC-C-deficient mice, effects of GPs are unaltered, which could be by new cGMP-independent signaling pathway (G-protein-coupled receptor). This is not unusual as atrial natriuretic peptide also activates two different types of receptors: guanylate cylcase A and clearance receptor which is also G-protein coupled receptor. Physiological role of GPs in other organs (liver, pancreas, lung, sweat glands, and male reproductive system) needs to be discovered. However, it is known that they are involved in pathological conditions like cystic fibrosis, asthma, intestinal tumors, kidney and heart failure, obesity, and metabolic syndrome.

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