Paola Guallini

Policlinico San Matteo Pavia Fondazione IRCCS, Ticinum, Lombardy, Italy

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Publications (9)36.9 Total impact

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    ABSTRACT: Until now, hepatocytes have been the only known cell source of macrophage-stimulating protein (MSP), and tissue macrophages have been the cells on which the biologic effects of MSP have been proved. To extend the understanding of the biologic meaning of MSP, it was investigated whether MSP operates in the kidney. MSP protein was evaluated by Western blot in supernatant of cultured human tubular cells (HK2) and human mesangial cells (HMC). MSP mRNA was investigated in HK2 by reverse transcription-polymerase chain reaction (RT-PCR). The expression of the MSP receptor, RON, was evaluated in HMC and HK2 by Western blot. RON mRNA was investigated in HMC by RT-PCR. The expression of MSP and RON in normal human renal tissue was studied by immunohistochemistry. HMC were stimulated with recombinant MSP (rMSP) and HK2 supernatant to study cell growth, migration, and the capacity to invade an artificial collagen matrix and synthesize interleukin-6 (IL-6). HK2 produced MSP and expressed RON in a form that was phosphorylated by rMSP. HMC expressed RON but did not produce MSP. MSP in HK2 supernatant and rMSP induced in HMC phosphorylation of RON, growth, migration, invasion, and IL-6 synthesis. In normal human kidney, tubules expressed MSP and RON. These results indicate a novel field of operation for MSP and suggest a pathogenic role of the MSP/RON system in renal disease. In fact, MSP released by tubular cells may recruit monocytes/macrophages in inflammatory tubulointerstitial disorders. In addition, MSP either circulating or as paracrine product may sustain glomerular mesangioproliferative disease.
    No preview · Article · Apr 2002 · Journal of the American Society of Nephrology
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    ABSTRACT: The HIV pandemic represents a new challenge to biomedical research. What began as a handful of recognized cases among homosexual men in the US has become a global pandemic of such proportions that it clearly ranks as one of the most destructive viral scourges in history. In the past few years new treatments and drugs have been developed and tested, but the development of a new generation of therapies remains a major priority, because of the lack of chemotherapeutic drugs or vaccines that show long-term efficacy in vivo. Recently, gene therapeutic strategies for the treatment of patients with HIV infection have received increased attention because they are able to offer the possibility of simultaneously targeting multiple sites in the HIV genome, thereby minimizing the production of resistant virus. Recombinant genes for gene therapy can be classified as expressing interfering proteins (intracellular antibodies, dominant negative proteins) or interfering RNAs (antisense RNAs, ribozymes, RNA decoys). The latter group offers the advantage of avoiding the stimulation of host immune response which might progressively decrease the efficacy of proteins. The stumbling block to achieving lasting antiviral effects is still represented by the lack of efficient gene transfer techniques capable of generating persistent transgene expression and a high number of transduced cells relative to untransduced cells. Novel delivery vectors, such as lentiviruses, might overcome some of these shortcomings. The use of recombinant genes to generate immunity is a very promising concept that is rapidly expanding. Since the immune system can significantly amplify the response to tiny amounts of antigen, DNA vaccines can indeed be delivered by exploiting traditional gene therapy approaches without the need of high transduction efficiency.
    No preview · Article · Feb 2002 · American Journal of PharmacoGenomics
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    ABSTRACT: Peritonitis causes mesothelial detachment that may result in persistent peritoneal denudation and fibrosis. We investigated whether hepatocyte growth factor (HGF), a scatter factor that induces detachment from substrate and fibroblastic transformation of several cell types, is produced during peritonitis and is active on mesothelial cells. We studied 18 patients on peritoneal dialysis, 9 uncomplicated, 9 with peritonitis. HGF was measured in serum, peritoneal fluid, and supernatant of peripheral blood mononuclear cells and peritoneal mononuclear cells. Primary culture of human peritoneal mesothelial cells and the human mesothelial cell line MeT-5A were conditioned with recombinant HGF, serum, and peritoneal fluid. HGF levels were significantly higher in serum and peritoneal fluid of peritonitic than uncomplicated patients. Mononuclear cells of peritonitic patients produced more HGF than cells of uncomplicated patients. Recombinant HGF, serum, and peritoneal fluid of peritonitic patients caused mesothelial cell growth, detachment, transformation from epithelial to fibroblast-like shape, overexpression of vimentin, and synthesis of type I and III collagen. In conclusion, HGF released during peritonitis causes a change in mesothelial cell phenotype and function. HGF may affect the healing process facilitating repair through mesothelial cell growth, but may contribute to peritoneal fibrosis inducing cell detachment with mesothelial denudation and collagen synthesis.
    Full-text · Article · Nov 2001 · American Journal Of Pathology
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    ABSTRACT: Hemodialysis prevents liver disease caused by hepatitis C virus: Role of hepatocyte growth factor. Hemodialysis increases markedly the serum levels of hepatocyte growth factor (HGF) so that regular dialysis treatment (RDT) mimics the regular administration of HGF as a drug. Therefore, we have studied the effects of dialysis-associated HGF production on the severity of liver damage caused by hepatitis C virus (HCV). Biochemical tests of liver function and liver biopsy were performed in 10 patients on RDT and in 11 patients without renal disease (WRD) converted to anti-HCV serum-positive test for the same time (48 +/- 4 months). The HGF serum concentration was measured by enzyme immunoassay. In patients on RDT, HGF was measured just before starting a dialysis session (T0), at 15 and 240 minutes of dialysis (T15 and T240), and 24 hours later (T24 hr). Serum HGF was similar in WRD (average 0.17 ng/ml) as in RDT at T0 (0.25 ng/ml). In RDT serum HGF increased markedly at T15 and T240 (5.51 and 2.67 ng/ml, respectively, P < 0. 001 vs. WRD and T0) and was still higher than baseline at T24 hr (0. 41 ng/ml, P < 0.05). Both grade of necroinflammatory activity and stage of fibrosis were significantly lower in RDT than in WRD (both, P < 0.001). The number of apoptotic hepatocytes was also significantly reduced in patients on RDT compared with patients WRD. These results show that HCV-related liver disease is more benign in patients on RDT. The phenomenon may depend on the marked and prolonged HGF release caused by dialysis.
    Full-text · Article · Jan 2000 · Kidney International

  • No preview · Article · May 1998 · Journal of chemotherapy (Florence, Italy)
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    ABSTRACT: Studies were performed in 26 patients on regular dialysis treatment with cuprophane (CU), polymethylmetacrilate (PMMA) or cuprammonium (CAM) dialyzers. Controls were six patients with chronic renal failure but not on regular dialysis treatment (CRF) and six healthy subjects (N). Blood was collected at the start (T0), and at 15 (T15) and 240 (T240) minutes of dialysis to measure the serum hepatocyte growth factor (HGF) concentration and to study HGF production by peripheral blood mononuclear cells (PBMC) in vitro. The form of HGF (that is, inactive/monomeric, active/dimeric) present in the serum was analyzed by immunoblotting. In addition, the ability of serum to stimulate proliferation of tubular cells (HK-2) and HGF release by PBMC and fibroblasts (MRC-5) was investigated. At T0, serum HGF levels were identical to that of the controls. In patients treated with CU, serum HGF rose from 0.24 ng/ml at T0 to 7.44 ng/ml at T15, and remained high at T240. PBMC collected at T15 and T240 released significantly more HGF in vitro than those collected at T0. Serum at T15 stimulated proliferation of HK-2 cells and the release of HGF by PBMC and MRC-5 cells. The PMMA and CAM dialyzers had similar effects as the CU. These results indicate that dialysis induces a striking rise in serum HGF and a prompt circulation of factor(s) stimulating HGF release. Dialysis-activated PBMC release HGF.
    Full-text · Article · May 1998 · Kidney International
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    ABSTRACT: We studied the role of free radicals on brain oxidative damage in rats after acute immobilization stress (restraint) and mild emotional stress (handling). To investigate brain oxidative damage, CuZn and Mn dependent superoxide dismutase (CuZn SOD, Mn SOD) activities, lipid peroxidation (TBARs), Na + K + ATPase activity, protein carbonyl (PrC), and reduced and oxidized glutathione (GSH, GSSG) levels were measured in the cerebral cortex (CTX), hippocampus (HIP), and striatum (ST) of the animals after the two different stress stimuli. Because stress produces abnormalities in the hypothalamic-pituitary-adrenal axis, the intensity of the two stress conditions were measured by plasmatic corticosteroid (COR) levels: particularly, COR levels doubled in handled rats and increased 15-fold in restrained animals. The SOD activities increased in CTX and decreased in HIP of the handled rats, while in ST a significant decrease in handled animals but an increase in restrained animals occurred. TBARs, GSH, and GSSG levels remained unchanged, while an index of glutathione redox decreased significantly in ST of handled animals and in CTX of restrained ones. Na + K + ATPase activity increased significantly in the HIP and ST of both groups of stressed rats. The stress induced a remarkable increase in PrC levels in all studied cerebral areas. These findings provide evidence to support the idea that stress produces oxidants but that the oxidative damage in stress differs in cerebral areas and could contribute to the degenerative mechanism of aging.
    Full-text · Article · Jan 1998 · International Journal of Stress Management

  • No preview · Article · Jul 1997 · Clinical Neurology and Neurosurgery
  • C Porta · M Moroni · P Guallini · C Torri · F Marzatico
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    ABSTRACT: Resistance to oxidative damage is an important feature of cancer cells. Cellular anti-radical enzymes, lipid peroxidation, glutathione pathway, capability to produce ROS, and cells' susceptibility to H2O2 and menadione toxicity, were analyzed in DND-1A and HeLa cancer cell lines. SOD and GSHPx activities were higher in DND-1A than in HeLa cells. Lipid peroxidation was the same in both cell lines, while menadione stimulation of ROS production was tenfold higher in HeLa cells. Total and reduced, but not oxidized, glutathione levels, were tenfold smaller in HeLa cells. H2O2 proved fatal to HeLa cells after 12 hours' incubation, while it was ineffective on DND-1A; DND-1A cells were more sensitive to menadione toxicity than HeLa cells. The two lines behaved differently in response to the above treatments. These observations might be important in designing more specific cancer treatments.
    No preview · Article · Sep 1996 · Anticancer research

Publication Stats

209 Citations
36.90 Total Impact Points


  • 2000-2002
    • Policlinico San Matteo Pavia Fondazione IRCCS
      • s.c. Cardiologia
      Ticinum, Lombardy, Italy
  • 1998-2002
    • University of Pavia
      Ticinum, Lombardy, Italy
  • 2001
    • INRCA Istituto Nazionale di Ricovero e Cura per Anziani
      Ancona, The Marches, Italy