Localization of urokinase-type plasminogen activator in human eyes: An immunocytochemical study

Tripathi, Ramesh C.; Tripathi, Brenda J.; Park, James K.

doi:10.1016/0014-4835(90)90085-9

Cited by 31 publications

(11 citation statements)

References 22 publications

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“…No uPAR was detected in the resident corneal stromal cells, keratocytes, lysed immediately after isolation (not grown in culture) ( Figure 4A, lane 1). The absence of immunodetected keratocyte uPAR confirms the in situ observation that uPAR is not expressed in the normal, unwounded corneal stroma (Tripathi et al, 1990). Full-length uPAR (D1D2D3) (HoyerHansen et al, 1992) was detected in fibroblasts grown in SSFM-FGF 72 h ( Figure 4A, lane 2).…”

Section: Upar Is Differentially Expressed In Keratocytes Fibroblastssupporting

confidence: 59%

Urokinase Receptor Cleavage: A Crucial Step in Fibroblast-to-Myofibroblast Differentiation

Bernstein¹,

Twining

Warejcka

et al. 2007

MBoC

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Fibroblasts migrate into and repopulate connective tissue wounds. At the wound edge, fibroblasts differentiate into myofibroblasts, and they promote wound closure. Regulated fibroblast-to-myofibroblast differentiation is critical for regenerative healing. Previous studies have focused on the role in fibroblasts of urokinase plasmingen activator/urokinase plasmingen activator receptor (uPA/uPAR), an extracellular protease system that promotes matrix remodeling, growth factor activation, and cell migration. Whereas fibroblasts have substantial uPA activity and uPAR expression, we discovered that cultured myofibroblasts eventually lost cell surface uPA/uPAR. This led us to investigate the relevance of uPA/uPAR activity to myofibroblast differentiation. We found that fibroblasts expressed increased amounts of full-length cell surface uPAR (D1D2D3) compared with myofibroblasts, which had reduced expression of D1D2D3 but increased expression of the truncated form of uPAR (D2D3) on their cell surface. Retaining full-length uPAR was found to be essential for regulating myofibroblast differentiation, because 1) protease inhibitors that prevented uPAR cleavage also prevented myofibroblast differentiation, and 2) overexpression of cDNA for a noncleavable form of uPAR inhibited myofibroblast differentiation. These data support a novel hypothesis that maintaining full-length uPAR on the cell surface regulates the fibroblast to myofibroblast transition and that down-regulation of uPAR is necessary for myofibroblast differentiation. INTRODUCTIONMyofibroblast differentiation from fibroblasts is a critical component of the healing process. Regenerative healing (without scarring) results from the successful execution of what have been characterized as three distinct phases of wound healing. In the first phase, fibroblasts that migrate into the wound secrete proteases, extracellular matrix (ECM) molecules, and growth factors. In the second phase, fibroblasts differentiate into nonmotile, wound-contracting myofibroblasts that also secrete ECM proteins and remodel the ECM (Jester et al., 1995;Mohan et al., 2003;Netto et al., 2005). In the third phase, after wound closure, myofibroblasts usually disappear by apoptosis (Desmouliere et al., 1995). Pathological states such as hypertrophic scars, liver cirrhosis, idiopathic lung fibrosis, and glomerulosclerosis are characterized by the persistence of myofibroblasts, which contribute to disease progression by overproduction of ECM and by excessive contraction (Desmouliere et al., 2003;Gabbiani, 2003).To better understand the molecular basis for the fibroblast to myofibroblast transition, we have focused on the role of the urokinase plasmingen activator (uPA) pathway during wound healing. uPA is an extracellular serine protease that binds to its receptor, uPAR, and generates plasmin from plasminogen at the cell-matrix interface. Plasmin is a broadspectrum protease that not only cleaves fibrin and other ECM proteins but also promotes cell migration by activating matrix-sequestered metallopr...

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Section: Upar Is Differentially Expressed In Keratocytes Fibroblastssupporting

confidence: 59%

Urokinase Receptor Cleavage: A Crucial Step in Fibroblast-to-Myofibroblast Differentiation

Bernstein¹,

Twining

Warejcka

et al. 2007

MBoC

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“…In many of the tissues examined, uPA appeared to coexist with tPA. Tripathi et al 15 investigated the presence of uPA in various structures of the human eye by using an immunohistochemical technique. A moderately intense to intermediate reaction product was seen in the anterior layers of the retina, a weak reaction product appeared in the posterior layers of the retina, and the retinal pigment epithelium contained both tPA and uPA.…”

Section: Discussionmentioning

confidence: 99%

Tissue Type Plasminogen Activator Facilitates NMDA-Receptor–Mediated Retinal Apoptosis through an Independent Fibrinolytic Cascade

Kumada¹,

Niwa

Hara

et al. 2005

Invest. Ophthalmol. Vis. Sci.

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“…The therapeutic success of argon laser trabeculectomy is mediated by activation and release of proinflammatory cytokines, especially TNFα and IL-1α from TM cells (Bradley et al, 2000), which “remodel” the TM tissue via activation of MMP3 (Fleenor et al, 2003, Alexander and Acott, 2003, Parshley et al, 1995). Urokinase and tissue plasminogen activators, which are also expressed in TM cells (Tripathi et al, 1990b, Park et al, 1987), help proteolytically convert the zymogen proMMPs to MMPs.…”

Section: Tm Cell Responses To Stress Hormones and Cytokinesmentioning

confidence: 99%

The many faces of the trabecular meshwork cell

Stamer

Clark

2017

Experimental Eye Research

202

215

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With the combined purpose of facilitating useful vision over a lifetime, a number of ocular cells have evolved specialized features not found elsewhere in the body. The trabecular meshwork (TM) cell at the irido-corneal angle, which is a key regulator of intraocular pressure, is no exception. Examination of cells in culture isolated from the human TM has shown that they are unique in many ways, displaying characteristic features of several different cell types. Thus, these neural crest derived cells display expression patterns and behaviors typical of endothelia, fibroblasts, smooth muscle and macrophages, owing to the multiple roles and two distinct environments where they operate to maintain intraocular pressure homeostasis. In most individuals, TM cells function normally over a lifetime in the face of persistent stressors, including phagocytic, oxidative, mechanical and metabolic stresses. Study of TM cells isolated from ocular hypertensive eyes has shown a compromised ability to perform their daily duties. This review highlights the many responsibilities of the TM cell and its challenges, progress in our understanding of TM biology over the past 30 years, as well as discusses unanswered questions about TM dysfunction that results in IOP dysregulation and glaucoma.

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Localization of urokinase-type plasminogen activator in human eyes: An immunocytochemical study

Cited by 31 publications

References 22 publications

Urokinase Receptor Cleavage: A Crucial Step in Fibroblast-to-Myofibroblast Differentiation

Urokinase Receptor Cleavage: A Crucial Step in Fibroblast-to-Myofibroblast Differentiation

Tissue Type Plasminogen Activator Facilitates NMDA-Receptor–Mediated Retinal Apoptosis through an Independent Fibrinolytic Cascade

The many faces of the trabecular meshwork cell

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