{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T22:04:36Z","timestamp":1780437876571,"version":"3.54.1"},"reference-count":39,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T00:00:00Z","timestamp":1678665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009053","name":"DBT Wellcome Trust India alliance","doi-asserted-by":"publisher","award":["IA\/CPHI\/15\/1\/502031"],"award-info":[{"award-number":["IA\/CPHI\/15\/1\/502031"]}],"id":[{"id":"10.13039\/501100009053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Autophagy is a cell\u2019s evolutionary conserved process for degrading and recycling cellular proteins and removing damaged organelles. There has been an increasing interest in identifying the basic cellular mechanism of autophagy and its implications in health and illness during the last decade. Many proteinopathies such as Alzheimer\u2019s and Huntington\u2019s disease are reported to be associated with impaired autophagy. The functional significance of autophagy in exfoliation syndrome\/exfoliation glaucoma (XFS\/XFG), remains unknown though it is presumed to be impaired autophagy to be responsible for the aggregopathy characteristic of this disease. In the current study we have shown that autophagy or ATG5 is enhanced in response to TGF-\u03b21 in human trabecular meshwork (HTM) cells and TGF-\u03b21 induced autophagy is necessary for increased expression of profibrotic proteins and epithelial to mesenchymal (EMT) through Smad3 that lead to aggregopathy. Inhibition of ATG5 by siRNA mediated knockdown reduced profibrotic and EMT markers and increased protein aggregates in the presence of TGF-\u03b21 stimulation. The miR-122-5p, which was increased upon TGF exposure, was also reduced upon ATG5 inhibition. We thus conclude that TGF-\u03b21 induces autophagy in primary HTM cells and a positive feedback loop exists between TGF-\u03b21 and ATG5 that regulated TGF downstream effects mainly mediated by Smad3 signaling with miR-122-5p also playing a role.<\/jats:p>","DOI":"10.3390\/cimb45030154","type":"journal-article","created":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T06:57:11Z","timestamp":1678777031000},"page":"2381-2392","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A Feedback Loop between TGF-\u03b21 and ATG5 Mediated by miR-122-5p Regulates Fibrosis and EMT in Human Trabecular Meshwork Cells"],"prefix":"10.3390","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0765-3146","authenticated-orcid":false,"given":"Munmun","family":"Chakraborthy","sequence":"first","affiliation":[{"name":"Hyderabad Eye Research Foundation (HERF), L.V. Prasad Eye Institute, Bhubaneswar 751024, Odisha, India"},{"name":"School of Biotechnology, KIIT University, Bhubaneswar 751024, Odisha, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aparna","family":"Rao","sequence":"additional","affiliation":[{"name":"Hyderabad Eye Research Foundation (HERF), L.V. Prasad Eye Institute, Bhubaneswar 751024, Odisha, India"},{"name":"School of Biotechnology, KIIT University, Bhubaneswar 751024, Odisha, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.2147\/OPTH.S254504","article-title":"Differential miRNA Expression: Signature for Glaucoma in Pseudoexfoliation","volume":"14","author":"Rao","year":"2020","journal-title":"Clin. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Sahay, P., Reddy, S., Prusty, B.K., Modak, R., and Rao, A. (2021). 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