@article {6681, title = {Extracellular Caspase-1 induces hair stem cell migration in wounded and inflamed skin conditions.}, journal = {J Cell Biol}, volume = {223}, year = {2024}, month = {2024 Jul 01}, abstract = {

The wound-healing process is a paradigm of the directed migration of various pools of stem cells from their niche to the site of injury where they replenish damaged cells. Two decades have elapsed since the observation that wounding activates multipotent hair follicle stem cells to infiltrate the epidermis, but the cues that coax these cells out of their niche remain unknown. Here, we report that Caspase-1, a protein classically known as an integral component of the cytosolic inflammasome, is secreted upon wounding and has a non-canonical role in the extracellular milieu. Through its caspase activation recruitment domain (CARD), Caspase-1 is sufficient to initiate the migration of hair follicle stem cells into the epidermis. Uncovering this novel function of Caspase-1 also facilitates a deeper understanding of the mechanistic basis of the epithelial hyperplasia found to accompany numerous inflammatory skin diseases.

}, keywords = {Animals, Caspase 1, Cell Movement, Dermatitis, Hair, Hair Follicle, Inflammation, Mice, Stem Cells, Wound Healing}, issn = {1540-8140}, doi = {10.1083/jcb.202306028}, author = {Hegde, Akshay and Ghosh, Subhasri and Ananthan, Akhil Shp and Kataria, Sunny and Dutta, Abhik and Prabhu, Srilekha and Khedkar, Sneha Uday and Dutta, Anupam and Jamora, Colin} } @article {6680, title = {TANGO1 inhibitors reduce collagen secretion and limit tissue scarring.}, journal = {Nat Commun}, volume = {15}, year = {2024}, month = {2024 Apr 24}, pages = {3302}, abstract = {

Uncontrolled secretion of ECM proteins, such as collagen, can lead to excessive scarring and fibrosis and compromise tissue function. Despite the widespread occurrence of fibrotic diseases and scarring, effective therapies are lacking. A promising approach would be to limit the amount of collagen released from hyperactive fibroblasts. We have designed membrane permeant peptide inhibitors that specifically target the primary interface between TANGO1 and cTAGE5, an interaction that is required for collagen export from endoplasmic reticulum exit sites (ERES). Application of the peptide inhibitors leads to reduced TANGO1 and cTAGE5 protein levels and a corresponding inhibition in the secretion of several ECM components, including collagens. Peptide inhibitor treatment in zebrafish results in altered tissue architecture and reduced granulation tissue formation during cutaneous wound healing. The inhibitors reduce secretion of several ECM proteins, including collagens, fibrillin and fibronectin in human dermal fibroblasts and in cells obtained from patients with a generalized fibrotic disease (scleroderma). Taken together, targeted interference of the TANGO1-cTAGE5 binding interface could enable therapeutic modulation of ERES function in ECM hypersecretion, during wound healing and fibrotic processes.

}, keywords = {Animals, Cicatrix, Collagen, Endoplasmic Reticulum, Extracellular Matrix, Fibroblasts, Fibrosis, Humans, Peptides, Scleroderma, Systemic, Skin, Wound Healing, Zebrafish}, issn = {2041-1723}, doi = {10.1038/s41467-024-47004-1}, author = {Raote, Ishier and Rosendahl, Ann-Helen and H{\"a}kkinen, Hanna-Maria and Vibe, Carina and K{\"u}{\c c}{\"u}kaylak, Ismail and Sawant, Mugdha and Keufgens, Lena and Frommelt, Pia and Halwas, Kai and Broadbent, Katrina and Cunquero, Marina and Castro, Gustavo and Villemeur, Marie and N{\"u}chel, Julian and Bornikoel, Anna and Dam, Binita and Zirmire, Ravindra K and Kiran, Ravi and Carolis, Carlo and Andilla, Jordi and Loza-Alvarez, Pablo and Ruprecht, Verena and Jamora, Colin and Campelo, Felix and Kr{\"u}ger, Marcus and Hammerschmidt, Matthias and Eckes, Beate and Neundorf, Ines and Krieg, Thomas and Malhotra, Vivek} } @article {3343, title = {Initiation of wound healing is regulated by the convergence of mechanical and epigenetic cues.}, journal = {PLoS Biol}, volume = {20}, year = {2022}, month = {2022 09}, pages = {e3001777}, abstract = {

Wound healing in the skin is a complex physiological process that is a product of a cell state transition from homeostasis to repair. Mechanical cues are increasingly being recognized as important regulators of cellular reprogramming, but the mechanism by which it is translated to changes in gene expression and ultimately cellular behavior remains largely a mystery. To probe the molecular underpinnings of this phenomenon further, we used the down-regulation of caspase-8 as a biomarker of a cell entering the wound healing program. We found that the wound-induced release of tension within the epidermis leads to the alteration of gene expression via the nuclear translocation of the DNA methyltransferase 3A (DNMT3a). This enzyme then methylates promoters of genes that are known to be down-regulated in response to wound stimuli as well as potentially novel players in the repair program. Overall, these findings illuminate the convergence of mechanical and epigenetic signaling modules that are important regulators of the transcriptome landscape required to initiate the tissue repair process in the differentiated layers of the epidermis.

}, keywords = {Biomarkers, Caspase 8, Cues, Epigenesis, Genetic, Wound Healing}, issn = {1545-7885}, doi = {10.1371/journal.pbio.3001777}, author = {Bhatt, Tanay and Dey, Rakesh and Hegde, Akshay and Ketkar, Alhad Ashok and Pulianmackal, Ajai J and Deb, Ashim P and Rampalli, Shravanti and Jamora, Colin} } @article {1160, title = {Cytoplasmic poly (A)-binding protein critically regulates epidermal maintenance and turnover in the planarian .}, journal = {Development}, volume = {144}, year = {2017}, month = {2017 09 01}, pages = {3066-3079}, abstract = {

Identifying key cellular events that facilitate stem cell function and tissue organization is crucial for understanding the process of regeneration. Planarians are powerful model system to study regeneration and stem cell (neoblast) function. Here, using planaria, we show that the initial events of regeneration, such as epithelialization and epidermal organization are critically regulated by a novel cytoplasmic poly A-binding protein, SMED-PABPC2. Knockdown leads to defects in epidermal lineage specification, disorganization of epidermis and ECM, and deregulated wound healing, resulting in the selective failure of neoblast proliferation near the wound region. Polysome profiling suggests that epidermal lineage transcripts, including , are translationally regulated by SMED-PABPC2 Together, our results uncover a novel role for SMED-PABPC2 in the maintenance of epidermal and ECM integrity, critical for wound healing and subsequent processes for regeneration.

}, keywords = {Animals, Cell Lineage, Cell Proliferation, Cytoplasm, Epidermis, Epithelium, Extracellular Matrix, Gene Knockdown Techniques, Homeostasis, Models, Biological, Planarians, Poly(A)-Binding Protein I, Regeneration, RNA, Messenger, Wound Healing}, issn = {1477-9129}, doi = {10.1242/dev.152942}, author = {Bansal, Dhiru and Kulkarni, Jahnavi and Nadahalli, Kavana and Lakshmanan, Vairavan and Krishna, Srikar and Sasidharan, Vidyanand and Geo, Jini and Dilipkumar, Shilpa and Pasricha, Renu and Gulyani, Akash and Raghavan, Srikala and Palakodeti, Dasaradhi} }