Skip to main content
Erschienen in: Archives of Dermatological Research 2/2017

11.01.2017 | Original Paper

Senescence in the lesional fibroblasts of non-segmental vitiligo patients

verfasst von: Seema Rani, Supriya Bhardwaj, Niharika Srivastava, Vijay Lakshmi Sharma, Davinder Parsad, Ravinder Kumar

Erschienen in: Archives of Dermatological Research | Ausgabe 2/2017

Einloggen, um Zugang zu erhalten

Abstract

Dermal fibroblasts secrete various growth factors which are important for skin pigmentation. Imbalance in the synchronization of epidermal and dermal cells in the skin can play vital role in the pathogenesis of pigmentary disorder vitiligo. Therefore, our objective was to check the lesional fibroblasts for any abnormality and senescence in non-segmental vitiligo patients (NSV). Skin punch biopsies were taken from NSV patients and healthy controls. Explant culture of fibroblast from lesional dermis, non-lesional dermis, and control was analyzed. The senescence was confirmed by β-galactosidase staining in the cultured fibroblasts. Senescence was checked at mRNA level in lesional dermis, non-lesional dermis of NSV patients by senescence markers p16, p21, and hp1 by quantitative real-time polymerase chain reaction (qRT-PCR) and immunofluorescence study was used for protein analysis. Morphological results showed number of fibroblasts with bigger perinuclear region and vacuoles were more in the lesional fibroblasts. Number of β-galactosidase positive fibroblasts in the lesional skin of NSV patients was higher as compared to the non-lesional and control fibroblasts. Results showed higher relative gene expression of senescence markers p16, p21, and hp1 in the lesional dermis of NSV patients at mRNA level and protein level as compared with control. Senescence in the dermal fibroblasts can decrease the secretion of growth factors and cytokines secreted by fibroblasts which may lead to the melanocyte death and progression of vitiligo. However, further studies on larger number of patients are needed to confirm the role of fibroblasts in the vitiligo pathogenesis.
Literatur
1.
Zurück zum Zitat Arias AM (2001) Epithelial mesenchymal interactions in cancer and development. Cell 105:425–431CrossRefPubMed Arias AM (2001) Epithelial mesenchymal interactions in cancer and development. Cell 105:425–431CrossRefPubMed
2.
Zurück zum Zitat Bayreuther K, Rodemann HP, Hommel R, Dittmann K, Albiez M, Francz PI (1988) Human skin fibroblasts in vitro differentiate along a terminal cell lineage. Proc Natl Acad Sci USA 85:5112–5116CrossRefPubMedPubMedCentral Bayreuther K, Rodemann HP, Hommel R, Dittmann K, Albiez M, Francz PI (1988) Human skin fibroblasts in vitro differentiate along a terminal cell lineage. Proc Natl Acad Sci USA 85:5112–5116CrossRefPubMedPubMedCentral
3.
4.
Zurück zum Zitat Camara-Lemarroy CR, Salas-Alanis JC (2013) The role of tumor necrosis factor-α in the pathogenesis of vitiligo. Am J Clin Dermatol 14:343CrossRefPubMed Camara-Lemarroy CR, Salas-Alanis JC (2013) The role of tumor necrosis factor-α in the pathogenesis of vitiligo. Am J Clin Dermatol 14:343CrossRefPubMed
5.
Zurück zum Zitat Cao L, Li W, Kim S, Brodie SG, Deng CX (2003) Senescence, aging and malignant transformation mediated by p53 in mice lacking the Brca1 full length isoform. Genes Dev 17(2):201–213CrossRefPubMedPubMedCentral Cao L, Li W, Kim S, Brodie SG, Deng CX (2003) Senescence, aging and malignant transformation mediated by p53 in mice lacking the Brca1 full length isoform. Genes Dev 17(2):201–213CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Castro P, Giri D, Lamb D, Ittmann M (2003) Cellular senescence in the pathogenesis of benign prostatic hyperplasia. Prostate 55(1):30–38CrossRefPubMed Castro P, Giri D, Lamb D, Ittmann M (2003) Cellular senescence in the pathogenesis of benign prostatic hyperplasia. Prostate 55(1):30–38CrossRefPubMed
7.
Zurück zum Zitat Chang HY, Sneddon JB, Alizadeh AA, Sood R, West RB, Montgomery K et al (2004) Gene expression signature of fibroblast serum response predicts human cancer progression: Similarities between tumors and wounds. PLoS Biol 2:E7CrossRefPubMedPubMedCentral Chang HY, Sneddon JB, Alizadeh AA, Sood R, West RB, Montgomery K et al (2004) Gene expression signature of fibroblast serum response predicts human cancer progression: Similarities between tumors and wounds. PLoS Biol 2:E7CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Choi W, Wolber R, Gerwat W, Mann T, Batzer J, Smuda C et al (2010) The fibroblast-derived paracrine factor neuregulin-1 has a novel role in regulating the constitutive color and melanocyte function in human skin. J Cell Sci 123:3102–3111CrossRefPubMedPubMedCentral Choi W, Wolber R, Gerwat W, Mann T, Batzer J, Smuda C et al (2010) The fibroblast-derived paracrine factor neuregulin-1 has a novel role in regulating the constitutive color and melanocyte function in human skin. J Cell Sci 123:3102–3111CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Clara CM, Graeme H, Joao F P (2014) Telomeres, oxidative stress and inflammatory factors: partners in cellular senescence? Longev Healthspan 3:1CrossRef Clara CM, Graeme H, Joao F P (2014) Telomeres, oxidative stress and inflammatory factors: partners in cellular senescence? Longev Healthspan 3:1CrossRef
10.
Zurück zum Zitat Collado M, Gil J, Efeyan A, Guerra C, Schuhmacher AJ, Barradas M et al (2005) Tumour biology: senescence in premalignant tumours. Nat 436(7051):642.CrossRef Collado M, Gil J, Efeyan A, Guerra C, Schuhmacher AJ, Barradas M et al (2005) Tumour biology: senescence in premalignant tumours. Nat 436(7051):642.CrossRef
11.
Zurück zum Zitat Dell’Anna ML, Urbanelli S, Mastrofrancesco A, Camera E, Iacovelli P, Leone G et al (2003) Alterations of mitochondria in peripheral blood monoculear cells of vitiligo patients. Pigment Cell Res 16:553–559CrossRefPubMed Dell’Anna ML, Urbanelli S, Mastrofrancesco A, Camera E, Iacovelli P, Leone G et al (2003) Alterations of mitochondria in peripheral blood monoculear cells of vitiligo patients. Pigment Cell Res 16:553–559CrossRefPubMed
12.
Zurück zum Zitat Dickson MA, Hahn WC, Ino Y, Ronfard V, Wu JY, Weinberg RA et al (2000) Human keratinocytes that express hTERT and also bypass a p16INK4a-enforced mechanism that limits life span become immortal yet retain normal growth and differentiation characteristics. Mol Cell Biol 20(4):1436–1447CrossRefPubMedPubMedCentral Dickson MA, Hahn WC, Ino Y, Ronfard V, Wu JY, Weinberg RA et al (2000) Human keratinocytes that express hTERT and also bypass a p16INK4a-enforced mechanism that limits life span become immortal yet retain normal growth and differentiation characteristics. Mol Cell Biol 20(4):1436–1447CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Gauthier Y, Cario Andre M, Taieb A (2003) A critical appraisal of vitiligo etiologic theories. Is melanocyte loss a melanocytorrhagy? Pigment Cell Res 16:322–332CrossRefPubMed Gauthier Y, Cario Andre M, Taieb A (2003) A critical appraisal of vitiligo etiologic theories. Is melanocyte loss a melanocytorrhagy? Pigment Cell Res 16:322–332CrossRefPubMed
14.
Zurück zum Zitat Giovannelli L, Bellandi S, Pitozzi V, Fabbri P, Dolara P, Moretti S (2004) Increased oxidative DNA damage in mononuclear leukocytes in vitiligo. Mutat Res 556:101–106CrossRefPubMed Giovannelli L, Bellandi S, Pitozzi V, Fabbri P, Dolara P, Moretti S (2004) Increased oxidative DNA damage in mononuclear leukocytes in vitiligo. Mutat Res 556:101–106CrossRefPubMed
15.
Zurück zum Zitat Glinka A, Wu W, Delius H, Monaghan AP, Blumenstock C, Niehrs C (1998). Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction. Nat 391:357–362CrossRef Glinka A, Wu W, Delius H, Monaghan AP, Blumenstock C, Niehrs C (1998). Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction. Nat 391:357–362CrossRef
16.
Zurück zum Zitat Helenius M, Makelainen L, Salminen A (1999) Attenuation of NF-kappaB signaling response to UVB light during cellular senescence. Exp Cell Res 248:194–202CrossRefPubMed Helenius M, Makelainen L, Salminen A (1999) Attenuation of NF-kappaB signaling response to UVB light during cellular senescence. Exp Cell Res 248:194–202CrossRefPubMed
17.
Zurück zum Zitat Imokawa G, Yada Y, Morisaki N, Kimura M (1998) Biological characterization of human fibroblast-derived mitogenic factors for human melanocytes. J Biochem 330:1235–1239CrossRef Imokawa G, Yada Y, Morisaki N, Kimura M (1998) Biological characterization of human fibroblast-derived mitogenic factors for human melanocytes. J Biochem 330:1235–1239CrossRef
18.
Zurück zum Zitat Itahana K, Campisi J, Dimri GP (2007) Methods to detect biomarkers of cellular senescence: the senescence-associated beta-galactosidase assay. Methods Mol Biol 371:21–31CrossRefPubMed Itahana K, Campisi J, Dimri GP (2007) Methods to detect biomarkers of cellular senescence: the senescence-associated beta-galactosidase assay. Methods Mol Biol 371:21–31CrossRefPubMed
19.
Zurück zum Zitat Kang MK, Bibb C, Baluda MA, Rey O, Park NH (2000) In vitro replication and differentiation of normal human oral keratinocytes. Exp Cell Res 258:288–297CrossRefPubMed Kang MK, Bibb C, Baluda MA, Rey O, Park NH (2000) In vitro replication and differentiation of normal human oral keratinocytes. Exp Cell Res 258:288–297CrossRefPubMed
20.
Zurück zum Zitat Kitamura R, Tsukamoto K, Harada K, Shimizu A, Shimada S, Kobayashi T et al (2004) Mechanisms underlying the dysfunction of melanocytes in vitiligo epidermis: role of SCF/KIT protein interactions and the downstream effector, MITF-M. J Pathol 202:463–475CrossRefPubMed Kitamura R, Tsukamoto K, Harada K, Shimizu A, Shimada S, Kobayashi T et al (2004) Mechanisms underlying the dysfunction of melanocytes in vitiligo epidermis: role of SCF/KIT protein interactions and the downstream effector, MITF-M. J Pathol 202:463–475CrossRefPubMed
21.
Zurück zum Zitat Kosar M, Bartkova J, Hubackova S, Hodny Z, Lukas J, Bartek J (2011) Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type and insult-dependent manner, and follow expression of p16ink4a. Cell Cycle 10(3):457–468CrossRefPubMed Kosar M, Bartkova J, Hubackova S, Hodny Z, Lukas J, Bartek J (2011) Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type and insult-dependent manner, and follow expression of p16ink4a. Cell Cycle 10(3):457–468CrossRefPubMed
22.
Zurück zum Zitat Krishnamurthy J, Torrice C, Ramsey MR, Kovalev GI, Al-Regaiey K, Su L et al (2004) Ink4a/Arf expression is a biomarker of aging. J Clin Invest 114:1299–1307CrossRefPubMedPubMedCentral Krishnamurthy J, Torrice C, Ramsey MR, Kovalev GI, Al-Regaiey K, Su L et al (2004) Ink4a/Arf expression is a biomarker of aging. J Clin Invest 114:1299–1307CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Lee AY, Kim NH, Choi WI, Youm YH (2005) Less keratinocyte-derived factors related to more keratinocyte apoptosis in depigmented than normally pigmented suction-blistered epidermis may cause passive melanocyte death in vitiligo. J Invest Dermatol 124:976–983CrossRefPubMed Lee AY, Kim NH, Choi WI, Youm YH (2005) Less keratinocyte-derived factors related to more keratinocyte apoptosis in depigmented than normally pigmented suction-blistered epidermis may cause passive melanocyte death in vitiligo. J Invest Dermatol 124:976–983CrossRefPubMed
24.
Zurück zum Zitat Lee AY, Youm YH, Kim NH, Yang H, Choi WI (2004) Keratinocytes in the depigmented epidermis of vitiligo are more vulnerable to trauma (suction) than keratinocytes in the normally pigmented epidermis, resulting in their apoptosis. Br J Dermatol 151:995–1003CrossRefPubMed Lee AY, Youm YH, Kim NH, Yang H, Choi WI (2004) Keratinocytes in the depigmented epidermis of vitiligo are more vulnerable to trauma (suction) than keratinocytes in the normally pigmented epidermis, resulting in their apoptosis. Br J Dermatol 151:995–1003CrossRefPubMed
25.
Zurück zum Zitat Loughran O, Malliri A, Owens D, Gallimore PH, Stanley MA, Ozanne B et al (1996) Association of CDKN2A/p16INK4A with human head and neck keratinocyte replicative senescence: relationship of dysfunction to immortality and neoplasia. Oncogene 13(3):561–568PubMed Loughran O, Malliri A, Owens D, Gallimore PH, Stanley MA, Ozanne B et al (1996) Association of CDKN2A/p16INK4A with human head and neck keratinocyte replicative senescence: relationship of dysfunction to immortality and neoplasia. Oncogene 13(3):561–568PubMed
26.
Zurück zum Zitat Matsumoto K, Okazaki H, Nakamura T (1992) Up-regulation of hepatocyte growth factor gene expression by interleukin-1 in human skin fibroblasts. Biochem Biophys Res Commun 188:235–243CrossRefPubMed Matsumoto K, Okazaki H, Nakamura T (1992) Up-regulation of hepatocyte growth factor gene expression by interleukin-1 in human skin fibroblasts. Biochem Biophys Res Commun 188:235–243CrossRefPubMed
27.
Zurück zum Zitat Melk A, Schmidt BM, Takeuchi O, Sawitzki B, Rayner DC, Halloran PF (2004) Expression of p16INK4a and other cell cycle regulator and senescence associated genes in aging human kidney. Kidney Int 65:510–520CrossRefPubMed Melk A, Schmidt BM, Takeuchi O, Sawitzki B, Rayner DC, Halloran PF (2004) Expression of p16INK4a and other cell cycle regulator and senescence associated genes in aging human kidney. Kidney Int 65:510–520CrossRefPubMed
28.
Zurück zum Zitat Meyskens FL Jr, Farmer P, Fruehauf JP (2001) Redox regulation in human melanocytes and melanoma. Pigment Cell Res 14(3):148–154CrossRefPubMed Meyskens FL Jr, Farmer P, Fruehauf JP (2001) Redox regulation in human melanocytes and melanoma. Pigment Cell Res 14(3):148–154CrossRefPubMed
29.
Zurück zum Zitat Mildner M, Mlitz V, Gruber F, Wojta J, Tschachler E (2007) Hepatocyte growth factor establishes autocrine and paracrine feedback loops for the protection of skin cells after UV irradiation. J Invest Dermatol 127:2637–2644CrossRefPubMed Mildner M, Mlitz V, Gruber F, Wojta J, Tschachler E (2007) Hepatocyte growth factor establishes autocrine and paracrine feedback loops for the protection of skin cells after UV irradiation. J Invest Dermatol 127:2637–2644CrossRefPubMed
30.
Zurück zum Zitat Moretti S, Fabbri P, Baroni G, Berti S, Bani D, Berti E et al (2009) Keratinocyte dysfunction in vitiligo epidermis: cytokine microenvironment and correlation to keratinocyte apoptosis. Histol Histopathol 24:849–857PubMed Moretti S, Fabbri P, Baroni G, Berti S, Bani D, Berti E et al (2009) Keratinocyte dysfunction in vitiligo epidermis: cytokine microenvironment and correlation to keratinocyte apoptosis. Histol Histopathol 24:849–857PubMed
31.
Zurück zum Zitat Moretti S, Spallanzani A, Amato L, Hautmann G, Gallerani I, Fabiani M et al (2002) New insight into the pathogenesis of vitiligo: Imbalance of epidermal cytokines at sites of lesions. Pigment Cell Res 15:87–92CrossRefPubMed Moretti S, Spallanzani A, Amato L, Hautmann G, Gallerani I, Fabiani M et al (2002) New insight into the pathogenesis of vitiligo: Imbalance of epidermal cytokines at sites of lesions. Pigment Cell Res 15:87–92CrossRefPubMed
32.
Zurück zum Zitat Oh SH, Kim JY, Kim MR, Do JE, Shin JY, Hann SK (2012) DKK1 is highly expressed in the dermis of vitiligo lesion: is there association between DKK1 and vitiligo? J Dermatol Sci 66:163–165CrossRefPubMed Oh SH, Kim JY, Kim MR, Do JE, Shin JY, Hann SK (2012) DKK1 is highly expressed in the dermis of vitiligo lesion: is there association between DKK1 and vitiligo? J Dermatol Sci 66:163–165CrossRefPubMed
33.
Zurück zum Zitat Paratore C, Goerich DE, Suter U, Wegner M, Sommer L (2001) Survival and glial fate acquisition of neural crest cells are regulated by an interplay between the transcription factor Sox10 and extrinsic combinatorial signaling. Development 128:3949–3961PubMed Paratore C, Goerich DE, Suter U, Wegner M, Sommer L (2001) Survival and glial fate acquisition of neural crest cells are regulated by an interplay between the transcription factor Sox10 and extrinsic combinatorial signaling. Development 128:3949–3961PubMed
34.
Zurück zum Zitat Purpura V, Persechino F, Belleudi F, Scrofani C, Raffa S, Persechino S et al (2014) Decreased expression of KGF/FGF7 and its receptor in pathological hypopigmentation. J Cell Mol Med 18:2553–2557CrossRefPubMedPubMedCentral Purpura V, Persechino F, Belleudi F, Scrofani C, Raffa S, Persechino S et al (2014) Decreased expression of KGF/FGF7 and its receptor in pathological hypopigmentation. J Cell Mol Med 18:2553–2557CrossRefPubMedPubMedCentral
35.
Zurück zum Zitat Rheinwald JG, Hahn WC, Ramsey MR, Wu JY, Guo Z, Tsao H et al (2002) A two-stage, p16INK4A- and p53-dependent keratinocyte senescence mechanism that limits replicative potential independent of telomere status. Mol Cell Biol 22(19):5157–5172CrossRefPubMedPubMedCentral Rheinwald JG, Hahn WC, Ramsey MR, Wu JY, Guo Z, Tsao H et al (2002) A two-stage, p16INK4A- and p53-dependent keratinocyte senescence mechanism that limits replicative potential independent of telomere status. Mol Cell Biol 22(19):5157–5172CrossRefPubMedPubMedCentral
36.
Zurück zum Zitat Sato N, Maehara N, Goggins M (2004) Gene expression profiling of tumor-stromal interactions between pancreatic cancer cells and stromal fibroblasts. Cancer Res 64:6950–6956CrossRefPubMed Sato N, Maehara N, Goggins M (2004) Gene expression profiling of tumor-stromal interactions between pancreatic cancer cells and stromal fibroblasts. Cancer Res 64:6950–6956CrossRefPubMed
37.
Zurück zum Zitat Schallreuter KU, Moore J, Wood JM, Beazley WD, Gaze DC et al (1999) In vivo and in vitro evidence for hydrogen peroxide (H2O2) accumulation in the epidermis of patients with vitiligo and its successful removal by a UVB-activated pseudocatalase. J Invetsig Dermatol Symp Proc 4:91–96CrossRef Schallreuter KU, Moore J, Wood JM, Beazley WD, Gaze DC et al (1999) In vivo and in vitro evidence for hydrogen peroxide (H2O2) accumulation in the epidermis of patients with vitiligo and its successful removal by a UVB-activated pseudocatalase. J Invetsig Dermatol Symp Proc 4:91–96CrossRef
38.
Zurück zum Zitat Schulz I, Mahler HC, Boiteux S, Epe B (2000) Oxidative DNA base damage induced by singlet oxygen and photosensitization: Recognition by repair endonucleases and mutagenicity. Mutation res 461(2):145–156CrossRefPubMed Schulz I, Mahler HC, Boiteux S, Epe B (2000) Oxidative DNA base damage induced by singlet oxygen and photosensitization: Recognition by repair endonucleases and mutagenicity. Mutation res 461(2):145–156CrossRefPubMed
39.
Zurück zum Zitat Serrano M, Lee H, Chin L, Cordon-Cardo C, Beacg D, DePinho RA (1996) Role of the Ink4a locus in tumor suppression and cell mortality. Cell 85:27–37CrossRefPubMed Serrano M, Lee H, Chin L, Cordon-Cardo C, Beacg D, DePinho RA (1996) Role of the Ink4a locus in tumor suppression and cell mortality. Cell 85:27–37CrossRefPubMed
40.
Zurück zum Zitat Singh M, Mansuri MS, Parasrampuria MA, Begum R (2016) Interleukin 1-α: A modulator of melanocyte homeostasis in vitiligo. Biochem Anal Biochem 5:273 Singh M, Mansuri MS, Parasrampuria MA, Begum R (2016) Interleukin 1-α: A modulator of melanocyte homeostasis in vitiligo. Biochem Anal Biochem 5:273
41.
Zurück zum Zitat Sun LQ, Lee DW, Zhang Q, Xiao W, Raabe EH, Meeker A et al (2004) Growth retardation and premature aging phenotypes in mice with disruption of the SNF2-like gene. Genes Dev 18(9):1035–1046CrossRefPubMedPubMedCentral Sun LQ, Lee DW, Zhang Q, Xiao W, Raabe EH, Meeker A et al (2004) Growth retardation and premature aging phenotypes in mice with disruption of the SNF2-like gene. Genes Dev 18(9):1035–1046CrossRefPubMedPubMedCentral
42.
Zurück zum Zitat Susuma O (2007) Abnormal mitosis and aberrant nuclear morphology in senescent human fibroblasts. In: Garvey RB (eds) New research on cell aging. Nova Science Publishers, New York, pp 65–81 Susuma O (2007) Abnormal mitosis and aberrant nuclear morphology in senescent human fibroblasts. In: Garvey RB (eds) New research on cell aging. Nova Science Publishers, New York, pp 65–81
43.
Zurück zum Zitat Taïeb A, Picardo M (2010) Epidemiology, definitions and classification. In: Picardo Mauro (ed) Vitiligo, springer, Berlin, pp 13–24CrossRef Taïeb A, Picardo M (2010) Epidemiology, definitions and classification. In: Picardo Mauro (ed) Vitiligo, springer, Berlin, pp 13–24CrossRef
44.
Zurück zum Zitat Wonseon C, Rainer W, Wolfram G, Tobias M, Jan B, Christoph S et al (2010) The fibroblast-derived paracrine factor neuregulin-1 has a novel role in regulating the constitutive color and melanocyte function in human skin. J Cell Sci 123:3102–3111CrossRef Wonseon C, Rainer W, Wolfram G, Tobias M, Jan B, Christoph S et al (2010) The fibroblast-derived paracrine factor neuregulin-1 has a novel role in regulating the constitutive color and melanocyte function in human skin. J Cell Sci 123:3102–3111CrossRef
Metadaten
Titel
Senescence in the lesional fibroblasts of non-segmental vitiligo patients
verfasst von
Seema Rani
Supriya Bhardwaj
Niharika Srivastava
Vijay Lakshmi Sharma
Davinder Parsad
Ravinder Kumar
Publikationsdatum
11.01.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Archives of Dermatological Research / Ausgabe 2/2017
Print ISSN: 0340-3696
Elektronische ISSN: 1432-069X
DOI
https://doi.org/10.1007/s00403-016-1713-0

Weitere Artikel der Ausgabe 2/2017

Archives of Dermatological Research 2/2017 Zur Ausgabe

Leitlinien kompakt für die Dermatologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Dermatologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.