PMID- 35994210
OWN - NLM
STAT- MEDLINE
DCOM- 20221121
LR  - 20221214
IS  - 1749-6632 (Electronic)
IS  - 0077-8923 (Linking)
VI  - 1517
IP  - 1
DP  - 2022 Nov
TI  - Claudin targeting as an effective tool for directed barrier modulation of the 
      viable epidermis.
PG  - 251-265
LID - 10.1111/nyas.14879 [doi]
AB  - Tight junction (TJ) formation is vital for epidermal barrier function. We aimed 
      to specifically manipulate TJ barriers in the reconstructed human epidermis (RHE) 
      by claudin-1 and -4 knockdown (KD) and by claudin-binding fusion proteins of 
      glutathione S-transferase and modified C-terminal fragments of Clostridium 
      perfringens enterotoxin (GST-cCPE). Impedance spectroscopy and tracer 
      permeability imaging were employed for functional barrier assessment and 
      investigation of claudin contribution. KD of claudin-1, but not claudin-4, 
      impaired the paracellular barrier in vitro. Similarly, claudin-binding GST-cCPE 
      variants weakened the paracellular but not the stratum corneum barrier. Combining 
      both TJ targeting methods, we found that claudin-1 targeting by GST-cCPE after 
      claudin-4 KD led to a marked decrease in paracellular barrier properties. 
      Conversely, after claudin-1 KD, GST-cCPE did not further impair the barrier. 
      Comparison of GST-cCPE variants with different claudin-1/claudin-4 affinities, 
      NHS-fluorescein tracer detection, and immunostaining of RHE paraffin sections 
      showed that GST-cCPE variants bind to extrajunctional claudin-1 and -4, which are 
      differentially distributed along the stratum basale-stratum granulosum axis. 
      GST-cCPE binding blocks these claudins, thereby specifically opening the 
      paracellular barrier of RHE. The data indicate a critical role for claudin-1 in 
      regulating paracellular permeability for ions and small molecules in the viable 
      epidermis. Claudin targeting is presented as a proof-of-concept for precise 
      barrier modulation.
CI  - (c) 2022 The Authors. Annals of the New York Academy of Sciences published by Wiley 
      Periodicals LLC on behalf of New York Academy of Sciences.
FAU - Beier, Laura-Sophie
AU  - Beier LS
AD  - Clinical Physiology/Nutritional Medicine, Medical Department, Division of 
      Gastroenterology, Infectiology, Rheumatology, Charite - Universitatsmedizin 
      Berlin, Berlin, Germany.
AD  - Laboratory of Mucosal Barrier Pathobiology, Department of Pathology, Brigham and 
      Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
FAU - Waldow, Ayk
AU  - Waldow A
AD  - Clinical Physiology/Nutritional Medicine, Medical Department, Division of 
      Gastroenterology, Infectiology, Rheumatology, Charite - Universitatsmedizin 
      Berlin, Berlin, Germany.
FAU - Khomeijani Farahani, Saeed
AU  - Khomeijani Farahani S
AD  - Clinical Physiology/Nutritional Medicine, Medical Department, Division of 
      Gastroenterology, Infectiology, Rheumatology, Charite - Universitatsmedizin 
      Berlin, Berlin, Germany.
FAU - Mannweiler, Roman
AU  - Mannweiler R
AD  - Clinical Physiology/Nutritional Medicine, Medical Department, Division of 
      Gastroenterology, Infectiology, Rheumatology, Charite - Universitatsmedizin 
      Berlin, Berlin, Germany.
FAU - Vidal-Y-Sy, Sabine
AU  - Vidal-Y-Sy S
AD  - Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf, 
      Hamburg, Germany.
FAU - Brandner, Johanna M
AU  - Brandner JM
AD  - Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf, 
      Hamburg, Germany.
FAU - Piontek, Jorg
AU  - Piontek J
AUID- ORCID: 0000-0002-0880-8915
AD  - Clinical Physiology/Nutritional Medicine, Medical Department, Division of 
      Gastroenterology, Infectiology, Rheumatology, Charite - Universitatsmedizin 
      Berlin, Berlin, Germany.
FAU - Gunzel, Dorothee
AU  - Gunzel D
AUID- ORCID: 0000-0002-7998-7164
AD  - Clinical Physiology/Nutritional Medicine, Medical Department, Division of 
      Gastroenterology, Infectiology, Rheumatology, Charite - Universitatsmedizin 
      Berlin, Berlin, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220822
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (Claudins)
RN  - 0 (Claudin-1)
RN  - 0 (Claudin-4)
RN  - 0 (Claudin-5)
SB  - IM
MH  - Humans
MH  - *Claudins/metabolism
MH  - Claudin-1/metabolism
MH  - Claudin-4/metabolism
MH  - *Epidermis/metabolism
MH  - Permeability
MH  - Tight Junctions/metabolism
MH  - Claudin-5/metabolism
OTO - NOTNLM
OT  - claudin targeting
OT  - epidermal barrier
OT  - epidermis
OT  - impedance spectroscopy
OT  - tight junctions
EDAT- 2022/08/23 06:00
MHDA- 2022/11/22 06:00
CRDT- 2022/08/22 11:26
PHST- 2022/08/23 06:00 [pubmed]
PHST- 2022/11/22 06:00 [medline]
PHST- 2022/08/22 11:26 [entrez]
AID - 10.1111/nyas.14879 [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 2022 Nov;1517(1):251-265. doi: 10.1111/nyas.14879. Epub 2022 
      Aug 22.