A bstract B etaig-h3 (βig-h3) is a secretory pro tein compo sed of fasciclin I-like repeats con tainin g sequ en ces that allo w s bind ing of integrins and glycosam in oglycan s in vivo . E xpression of βig -h3 is respon sive to T G F-β an d the p rotein is found to be associated w ith extracellular m atrix (E C M ) m o lecu les, im p licatin g βig-h3 as an E C M adhesive pro tein o f d evelopm ental processes. W e p reviou sly observed p red om inant expression of βig-h3 expression in the basem ent m embrane o f proxim al tubu les o f kid ney. In this stu dy, the p hysio logical relevance of su ch localized expression of βig-h3 was exam ined in the renal proxim al tubular epithelial cells (RPTEC). R P T E C constitu tively exp ressed βig -h 3 and the exp ression w as dram atically ind uced b y exogenous TG F-β1 treatm ent. βig-h3 and its second and fou rth F A S 1 dom ain w ere able to m ed iate R P TE C adhesion, spreading and m igration. Tw o know n α3β1 integrin-interaction m otifs including aspartatic acid and isoleucine resid ues, N K D IL an d E P D IM in βig -h 3 w ere resp o n sib le to m ed iate R P T E C ad hesio n, sp readin g, an d m igratio n. B y using specific an tib odies against in tegrin s, w e confirm ed that α3 β1 in teg rin m ed iates th e adh esion and m ig ration of R P T E C s on βig -h 3. In ad dition, it also en hanced proliferation of R P TE C s th roug h N K D IL and E P D IM . These results ind icate th at βig-h3 m ediates adh esion , spreading, m igration and proliferation of R P TE C s th ro u g h th e in teractio n w ith α3β1 in teg rin an d is in tim ately in vo lved in th e m ain ten an ce an d the regeneratio n o f ren al proxim al tubu lar ep ith eliu m .
The concentrations of fibronectin in aqueous humor, measured by ELISA which was developed to detect fibronectin, ranged from 5 ng/ml to 100 ng/ml. Aqueous humor was aspirated from human eyes with cataracts and glaucomas using a 26 gauge needle through the peripheral cornea before making the limbal incision into the anterior chamber during surgery. The results of the study show that the average concentration and standard deviation of fibronectin was 0.136 +/- 0.192 microgram/ml in cataract eyes, and 0.962 +/- 0.918 microgram/ml in glaucoma eyes respectively. There was a statistically significant difference between both groups (p = 0.000). However, no significant differences according to age and sex were noted. There was no influence due to preoperative intravenous mannitol injection on fibronectin concentration. The source of aqueous fibronectin is still not clearly known and the mechanism of the higher concentration of fibronectin in glaucoma has not been clearly disclosed, however it is thought that normally present fibronectin is accumulated in the anterior chamber because it can not pass the aqueous outflow pathway, or that fibronectin production may be increased in glaucoma.
Topical fibronectin, autologous and homologous, was used to treat nine patients (eleven eyes) with persistent corneal epithelial defects and corneal ulcers that failed to improve with standard therapy. The fibronectin was purified from autologous and homologous plasma by gelatin-Sepharose 4B affinity chromatography and administered topically, 500 micrograms/ml five times a day, for three weeks. Complete or nearly complete reepithelialization was achieved in all patients regardless of the source of fibronectin, autologous or homologous. But healing times varied. The average healing time was 41.7 +/- 14.7 days (35.7 +/- 12.4 days for autologous, 50.8 +/- 14.4 days for homologous). Ocular symptoms were relieved significantly, and no side effects were observed. Over an average follow-up period of 5.2 months, no recurrences were noted. The results showed that homologous, as well as autologous, fibronectin was effective in patients with persistent corneal epithelial defects and corneal ulcers.
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