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Mindin is essential for cutaneous fibrogenesis in a new mouse model of systemic sclerosis [article]

Isha Rana, Sunny Kataria, Tuan Lin Tan, Edries Yousaf Hajam, Deepak Kumar Kashyap, Dyuti Saha, Johan Ajnabi, Sayan Paul, Shashank Jayappa, Akhil SHP Ananthan, Pankaj Kumar, Rania F. Zaarour (+11 others)
2022 bioRxiv   pre-print

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https://web.archive.org/web/20220527094127/https://www.biorxiv.org/content/biorxiv/early/2022/01/28/2022.01.26.477822.full.pdf

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ABSTRACTFibrosis is a result of chronically activated fibroblasts leading to the overproduction of extracellular matrix (ECM), causing tissue hardening and loss of organ function. Systemic sclerosis (SSc) is a fibrotic skin disease marked by inflammation, autoimmunity and vasculopathy along with progressive fibrosis of the skin and internal organs. A major bottleneck in understanding the etiology of SSc has been the lack of a holistic animal model that can mimic the human SSc disease. We found
more » ... hat the transcription factor Snail is overexpressed in the epidermis of SSc patients and a transgenic mouse recapitulating this expression pattern is sufficient to induce hallmark clinical features of the human disease. Using this mouse model as a discovery platform, we have uncovered a critical role for the matricellular protein Mindin in fibrogenesis. Mindin is produced by Snail transgenic skin keratinocytes and aids fibrogenesis by inducing inflammatory cytokine and collagen production in resident dermal fibroblasts. Given the dispensability of Mindin in normal tissue physiology, targeting this protein holds promise as an effective therapy for fibrosis.
doi:10.1101/2022.01.26.477822 fatcat:7i57o44i4bentklfg5miycklv4
Citation

Isha Rana, Sunny Kataria, Tuan Lin Tan, Edries Yousaf Hajam, Deepak Kumar Kashyap, Dyuti Saha, Johan Ajnabi, Sayan Paul, Shashank Jayappa, Akhil SHP Ananthan, Pankaj Kumar, Rania F. Zaarour, Haarshaadri J, Rekha Samuel, Renu George, Debashish Danda, Paul Mazhuvanchary Jacob, Rakesh Dey, Perundurai S Dhandapany, You-Wen He, John Varga, Shyni Varghese, Colin Jamora. "Mindin is essential for cutaneous fibrogenesis in a new mouse model of systemic sclerosis." bioRxiv (2022)