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Regulation of paracellular permeability: factors and mechanisms

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Abstract

Epithelial permeability is composed of transcellular permeability and paracellular permeability. Paracellular permeability is controlled by tight junctions (TJs). Claudins and occludin are two major transmembrane proteins in TJs, which directly determine the paracellular permeability to different ions or large molecules. Intracellular signaling pathways including Rho/Rho-associated protein kinase, protein kinase Cs, and mitogen-activated protein kinase, modulate the TJ proteins to affect paracellular permeability in response for diverse stimuli. Cytokines, growth factors and hormones in organism can regulate the paracellular permeability via signaling pathway. The transcellular transporters such as Na-K-ATPase, Na+-coupled transporters and chloride channels, can interact with paracellular transport and regulate the TJs. In this review, we summarized the factors affecting paracellular permeability and new progressions of the related mechanism in recent studies, and pointed out further research areas.

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Abbreviations

BBB:

Blood brain barrier

BTB:

Blood testis barrier

CFTR:

Cystic fibrosis transmembrane conductance regulator

ECL:

Extracellular loops

EGF:

Epidermal growth factor

ERK:

Extracellular signal-related kinases

GAPs:

GTPase activating proteins

GEFs:

Guanine nucleotide exchange factors

GUK:

Guanylate kinase

JAM:

Junctional adhesion molecule

JNK:

c-Jun amino-terminal kinases

MAGUK:

Membrane-associated guanylate kinases

MARVEL:

MAL and related proteins for vesicle trafficking and membrane link

MAPK:

Mitogen-activated protein kinase

MLC:

Myosin light chain

MLCK:

Myosin light chain kinase

NHE:

Sodium–hydrogen exchanger

PDGF:

Platelet-derived growth factor

PKCs:

Protein kinase Cs

ROCK:

Rho/Rho-associated protein kinase

SGLT:

Sodium–glucose transporters

TER:

Transepithelial electrical resistance

TGF:

Transforming growth factor

TJs:

Tight junctions

VEGF:

Vascular endothelial growth factor

ZO:

Zonula occludens

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Acknowledgments

We are indebted to all members of the Sperm Laboratory at Zhejiang University for their enlightening discussion. This project was supported in part by Zhejiang Provincial Natural Science Foundation of China (Grant No. Y2080362), the National Natural Science Foundation of China (Nos. 81100393 and 41276151), and Zhejiang Provincial Natural Science Foundation of China (Grant No. Y2100296).

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Authors and Affiliations

  1. Department of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, People’s Republic of China

    Yan-Jun Hu, Yi-Dong Wang & Wan-Xi Yang

  2. The Sperm Laboratory, Institute of Cell and Developmental Biology, College of Life Sciences, Zhejiang University, 866 Yu Hang Tang Road, Hangzhou, 310058, People’s Republic of China

    Yi-Dong Wang & Wan-Xi Yang

  3. The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, People’s Republic of China

    Fu-Qing Tan

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  1. Yan-Jun Hu
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  2. Yi-Dong Wang
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Correspondence to Wan-Xi Yang.

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Yan-Jun Hu and Yi-Dong Wang contributed equally to this study.

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Hu, YJ., Wang, YD., Tan, FQ. et al. Regulation of paracellular permeability: factors and mechanisms. Mol Biol Rep 40, 6123–6142 (2013). https://doi.org/10.1007/s11033-013-2724-y

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