BACKGROUND: Excessive basement membrane (BM) deposition in skin and mucosa is characteristic for lipoid proteinosis (LP; hyalinosis cutis et mucosae), an inherited disease caused by extracellular matrix protein 1 (ECM1) mutations. According to ultrastructure there are striking differences between junctional and microvascular BM. OBJECTIVE: Distinct analysis of the junctional zone in epidermis and oral mucosa, contrasting concentric BM arrays in the microvasculature; evaluation of impact on epithelial histogenesis and differentiation, and specifically on adhesion structures to BM (hemidesmosomes). METHODS: LP-epithelia were analyzed for alterations in differentiation, BM composition and texture, and hemidesmosomal components by indirect immunofluorescence (IIF), electron microscopy (EM), and immunoelectron microscopy (ImEM). RESULTS: Most striking was the irregular deposition of collagen IV and VII, BM-laminin, and laminin-5 at the junctional zone, accompanied by lamellate or punctuated structures below BM (IIF), whereas integrin alpha6beta4 and bullous pemphigoid antigen-1 and -2 (BPAG-1/-2) were regularly aligned. Also integrins alpha2beta1 and alpha3beta1 remained restricted to the epidermal basal layer, while the tissue-specific differentiation markers keratin K1/10 (mucosa, additionally K4/13) appeared delayed indicating mild hyperplasia, further confirmed by focal K6/16 expression. Ultrastructure (EM) disclosed abundance of extended basal cell protrusions and junctional aberrations like exfoliating excessive BM material. Hemidesmosomes were complete, but ImEM indicated weakened interactions between their components (BPAG-1, -2, and HD1). Confirming IIF, collagen IV and VII, and laminin-5 appeared extensively scattered, the latter two probably remaining associated. CONCLUSIONS: Subtle defects in anchorage assembly, spanning the entire BM zone, apparently compromise epithelial-matrix adhesion, which may provoke (mechanical stress-induced) erroneous BM repair.
BACKGROUND: Excessive basement membrane (BM) deposition in skin and mucosa is characteristic for lipoid proteinosis (LP; hyalinosis cutis et mucosae), an inherited disease caused by extracellular matrix protein 1 (ECM1) mutations. According to ultrastructure there are striking differences between junctional and microvascular BM. OBJECTIVE: Distinct analysis of the junctional zone in epidermis and oral mucosa, contrasting concentric BM arrays in the microvasculature; evaluation of impact on epithelial histogenesis and differentiation, and specifically on adhesion structures to BM (hemidesmosomes). METHODS: LP-epithelia were analyzed for alterations in differentiation, BM composition and texture, and hemidesmosomal components by indirect immunofluorescence (IIF), electron microscopy (EM), and immunoelectron microscopy (ImEM). RESULTS: Most striking was the irregular deposition of collagen IV and VII, BM-laminin, and laminin-5 at the junctional zone, accompanied by lamellate or punctuated structures below BM (IIF), whereas integrin alpha6beta4 and bullous pemphigoid antigen-1 and -2 (BPAG-1/-2) were regularly aligned. Also integrins alpha2beta1 and alpha3beta1 remained restricted to the epidermal basal layer, while the tissue-specific differentiation markers keratin K1/10 (mucosa, additionally K4/13) appeared delayed indicating mild hyperplasia, further confirmed by focal K6/16 expression. Ultrastructure (EM) disclosed abundance of extended basal cell protrusions and junctional aberrations like exfoliating excessive BM material. Hemidesmosomes were complete, but ImEM indicated weakened interactions between their components (BPAG-1, -2, and HD1). Confirming IIF, collagen IV and VII, and laminin-5 appeared extensively scattered, the latter two probably remaining associated. CONCLUSIONS:Subtle defects in anchorage assembly, spanning the entire BM zone, apparently compromise epithelial-matrix adhesion, which may provoke (mechanical stress-induced) erroneous BM repair.
Authors: Eric D Larson; Jose Pedrito M Magno; Matthew J Steritz; Erasmo Gonzalo D V Llanes; Jonathan Cardwell; Melquiadesa Pedro; Tori Bootpetch Roberts; Elisabet Einarsdottir; Rose Anne Q Rosanes; Christopher Greenlee; Rachel Ann P Santos; Ayesha Yousaf; Sven-Olrik Streubel; Aileen Trinidad R Santos; Amanda G Ruiz; Sheryl Mae Lagrana-Villagracia; Dylan Ray; Talitha Karisse L Yarza; Melissa A Scholes; Catherine B Anderson; Anushree Acharya; Samuel P Gubbels; Michael J Bamshad; Stephen P Cass; Nanette R Lee; Rehan S Shaikh; Deborah A Nickerson; Karen L Mohlke; Jeremy D Prager; Teresa Luisa G Cruz; Patricia J Yoon; Generoso T Abes; David A Schwartz; Abner L Chan; Todd M Wine; Eva Maria Cutiongco-de la Paz; Norman Friedman; Katerina Kechris; Juha Kere; Suzanne M Leal; Ivana V Yang; Janak A Patel; Ma Leah C Tantoco; Saima Riazuddin; Kenny H Chan; Petri S Mattila; Maria Rina T Reyes-Quintos; Zubair M Ahmed; Herman A Jenkins; Tasnee Chonmaitree; Lena Hafrén; Charlotte M Chiong; Regie Lyn P Santos-Cortez Journal: Hum Mutat Date: 2019-05-21 Impact factor: 4.878
Authors: Li Kong; Qingyun Tian; Fengjin Guo; Maria T Mucignat; Roberto Perris; Sandy Sercu; Joseph Merregaert; Paul E Di Cesare; Chuan-Ju Liu Journal: Matrix Biol Date: 2010-02-04 Impact factor: 11.583
Authors: Paramananda Saikia; Carla S Medeiros; Shanmugapriya Thangavadivel; Steven E Wilson Journal: Cell Tissue Res Date: 2018-10-03 Impact factor: 5.249