Polyphosphate, the physiological metabolic fuel for corneal cells: a potential biomaterial for ocular surface repair

Wang, Xiaohong; Gericke, Adrian; Ackermann, Maximilian; Wang, Shunfeng; Neufurth, Meik; Schröder, Heinz C.; Pfeiffer, Norbert; Müller, Wernér E.G.

doi:10.1039/c9bm01289c

Cited by 6 publications

(7 citation statements)

References 52 publications

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“…This finding will contribute to a further rational application of this drug during the initiation of lung toxicity, fibrosis, also with respect to a use of BLM in the treatment schedule in COVID-19 patients. In one in vivo study, using the dextran sodium sulfate (DSS)-induced chronic colitis model in mice, it had been disclosed that polyP ameliorate fibrosis in vivo in the mouse model [ 92 ]. The gathered data showed that poly P suppresses intestinal inflammation and fibrosis through downregulating of the expression of inflammation- and fibrosis-associated molecules in the intestinal epithelium [ 44 , 92 ].…”

Section: Discussionmentioning

confidence: 99%

“…In one in vivo study, using the dextran sodium sulfate (DSS)-induced chronic colitis model in mice, it had been disclosed that polyP ameliorate fibrosis in vivo in the mouse model [ 92 ]. The gathered data showed that poly P suppresses intestinal inflammation and fibrosis through downregulating of the expression of inflammation- and fibrosis-associated molecules in the intestinal epithelium [ 44 , 92 ]. Furthermore, it had been published that the CXCL14/CXCR4 chemokine axis is involved in the progression and/or activation of fibroblasts during initiation of pulmonary fibrosis in the lung [ 93 ].…”

Section: Discussionmentioning

confidence: 99%

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Polyphosphate Reverses the Toxicity of the Quasi-Enzyme Bleomycin on Alveolar Endothelial Lung Cells In Vitro

Müller

Neufurth

Wang

et al. 2021

Cancers

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The anti-cancer antitumor antibiotic bleomycin(s) (BLM) induces athyminic sites in DNA after its activation, a process that results in strand splitting. Here, using A549 human lung cells or BEAS-2B cells lunc cells, we show that the cell toxicity of BLM can be suppressed by addition of inorganic polyphosphate (polyP), a physiological polymer that accumulates and is released from platelets. BLM at a concentration of 20 µg ml−1 causes a decrease in cell viability (by ~70%), accompanied by an increased DNA damage and chromatin expansion (by amazingly 6-fold). Importantly, the BLM-caused effects on cell growth and DNA integrity are substantially suppressed by polyP. In parallel, the enlargement of the nuclei/chromatin in BLM-treated cells (diameter, 20–25 µm) is normalized to ~12 µm after co-incubation of the cells with BLM and polyP. A sequential application of the drugs (BLM for 3 days, followed by an exposure to polyP) does not cause this normalization. During co-incubation of BLM with polyP the gene for the BLM hydrolase is upregulated. It is concluded that by upregulating this enzyme polyP prevents the toxic side effects of BLM. These data might also contribute to an application of BLM in COVID-19 patients, since polyP inhibits binding of SARS-CoV-2 to cellular ACE2.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Polyphosphate Reverses the Toxicity of the Quasi-Enzyme Bleomycin on Alveolar Endothelial Lung Cells In Vitro

Müller

Neufurth

Wang

et al. 2021

Cancers

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“…Human immature dental pulp stem cells (hIDPSCs) express similar key characteristics as LESCs, such as ABCG2, integrin β1, p63, Cx43, and K3/12, indicating a potential alternative cell source for corneal reconstruction [ 295 ]. Moreover, inorganic polyphosphate (polyP) was demonstrated to increase cell viability/growth and migration of corneal epithelial cells, providing a potential biomaterial to treat LSCD [ 296 ]. Wang et al suggested that the water-soluble Na-polyP can be used as a biomimetic tear fluid to restore the corneal surface [ 296 ].…”

Section: Therapy Of Lscdmentioning

confidence: 99%

“…Moreover, inorganic polyphosphate (polyP) was demonstrated to increase cell viability/growth and migration of corneal epithelial cells, providing a potential biomaterial to treat LSCD [ 296 ]. Wang et al suggested that the water-soluble Na-polyP can be used as a biomimetic tear fluid to restore the corneal surface [ 296 ]. Except from polyP, many other substances are reported to have potential functions in improving corneal regeneration, such as trehalose, polymer 2-methacryloyloxyethyl phosphorylcholine (poly-MPC), glycoprotein 340, ferrostatin-1, agrin, fiber-reinforced gelatin methacrylate hydrogel, and keratan sulfate [ 297 , 298 , 299 , 300 , 301 , 302 ].…”

Section: Therapy Of Lscdmentioning

confidence: 99%

Corneal Epithelial Stem Cells–Physiology, Pathophysiology and Therapeutic Options

Ruan

Jiang

Musayeva

et al. 2021

Cells

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In the human cornea, regeneration of the epithelium is regulated by the stem cell reservoir of the limbus, which is the marginal region of the cornea representing the anatomical and functional border between the corneal and conjunctival epithelium. In support of this concept, extensive limbal damage, e.g., by chemical or thermal injury, inflammation, or surgery, may induce limbal stem cell deficiency (LSCD) leading to vascularization and opacification of the cornea and eventually vision loss. These acquired forms of limbal stem cell deficiency may occur uni- or bilaterally, which is important for the choice of treatment. Moreover, a variety of inherited diseases, such as congenital aniridia or dyskeratosis congenita, are characterized by LSCD typically occurring bilaterally. Several techniques of autologous and allogenic stem cell transplantation have been established. The limbus can be restored by transplantation of whole limbal grafts, small limbal biopsies or by ex vivo-expanded limbal cells. In this review, the physiology of the corneal epithelium, the pathophysiology of LSCD, and the therapeutic options will be presented.

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“…Earlier seminal works by Arthur Kornberg demonstrated that inorganic polyphosphate plays critical roles in several organisms, particularly in bacteria and yeast [6][7][8][9][10]. In the recent years, a plethora of important functions of this homopolymer have been highlighted in the context of various mammalian systems [11][12][13][14][15][16][17][18][19][20][21]. Among numerous functions of polyP, one of the Research Paper most evolutionary fascinating is its contribution to energy metabolism [15,[22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Inorganic polyphosphate as an energy source in tumorigenesis

et al. 2020

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Cancer cells have high demands for energy to maintain their exceedingly proliferative growth. However, the mechanism of energy expenditure in cancer is not well understood. We hypothesize that cancer cells might utilize energyrich inorganic polyphosphate (polyP), as energetic reserve. PolyP is comprised of orthophosphates linked by phosphoanhydride bonds, as in ATP. Here, we show that polyP is highly abundant in several types of cancer cells, including brain tumorinitiating cells (BTICs), i.e., stem-like cells derived from a mouse brain tumor model that we have previously described. The polymer is avidly consumed during starvation of the BTICs. Depletion of ATP by inhibiting glycolysis and mitochondrial ATP-synthase (OXPHOS) further decreases the levels of polyP and alters morphology of the cells. Moreover, enzymatic hydrolysis of the polymer impairs the viability of cancer cells and significantly deprives ATP stores. These results suggest that polyP might be utilized as a source of phosphate energy in cancer. While the role of polyP as an energy source is established for bacteria, this finding is the first demonstration that polyP may play a similar role in the metabolism of cancer cells.

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Polyphosphate, the physiological metabolic fuel for corneal cells: a potential biomaterial for ocular surface repair

Abstract: Polyphosphate, a natural inorganic polymer that acts as a reservoir for metabolic fuel (ATP), increases the proliferation and migration potency of epithelial cells, covering the avascular cornea.

Cited by 6 publications

References 52 publications

Polyphosphate Reverses the Toxicity of the Quasi-Enzyme Bleomycin on Alveolar Endothelial Lung Cells In Vitro

Polyphosphate Reverses the Toxicity of the Quasi-Enzyme Bleomycin on Alveolar Endothelial Lung Cells In Vitro

Corneal Epithelial Stem Cells–Physiology, Pathophysiology and Therapeutic Options

Inorganic polyphosphate as an energy source in tumorigenesis

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