An interplay of microglia and matrix metalloproteinase MMP9 under hypoxic stress regulates the opticin expression in retina
Abstract Inflammation plays a key role in the pathogenesis of retinal vascular diseases. We have shown earlier an increase in the activity of matrix metalloproteinases in the vitreous and tears of preterm born babies with retinopathy of prematurity (ROP) compared to those with no-ROP leading to a sh...
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2021
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oai:doaj.org-article:a0957f7a3b37412eb9e936c5d954316e2021-12-02T13:26:37ZAn interplay of microglia and matrix metalloproteinase MMP9 under hypoxic stress regulates the opticin expression in retina10.1038/s41598-021-86302-22045-2322https://doaj.org/article/a0957f7a3b37412eb9e936c5d954316e2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86302-2https://doaj.org/toc/2045-2322Abstract Inflammation plays a key role in the pathogenesis of retinal vascular diseases. We have shown earlier an increase in the activity of matrix metalloproteinases in the vitreous and tears of preterm born babies with retinopathy of prematurity (ROP) compared to those with no-ROP leading to a shift in the balance of angiogenic (vascular endothelial growth factor [VEGF], matrix metalloproteinase [MMPs], complement component [C3]) and anti-angiogenic (opticin, thrombospondin) in ROP eyes. We now confirmed that tear MMP levels in premature infants perfectly correlates with disease severity. Next, we demonstrated that a reduced opticin levels in ROP vitreous are regulated by MMPs secreted by activated microglia. Upon exposing the human microglia cell line (CHME3) to hypoxia, an increased expression of inflammatory proteins (MMP9, VEGF) was noticed while opticin reduced significantly (p = 0.005). Further, the reduced opticin’s expression by microglial cells under hypoxia could be rescued by inhibiting the MMP activity using doxycycline and EDTA. The inhibition of MMP activity altered the expression of other key signaling molecules under hypoxia. Our study clearly explains that increased activity of MMPs under hypoxia regulates the expression of opticin as seen in the vitreous humor of ROP and could serve as a potential target for ROP management.Satish PatnaikMeenakshi RaiSubhadra JalaliKomal AgarwalAkshay BadakereLavanya PuppalaSushma VishwakarmaDivya BalakrishnanPadmaja K. RaniRamesh KekunnayaPreeti Patil ChhablaniSubhabrata ChakrabartiInderjeet KaurNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) |
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Medicine R Science Q Satish Patnaik Meenakshi Rai Subhadra Jalali Komal Agarwal Akshay Badakere Lavanya Puppala Sushma Vishwakarma Divya Balakrishnan Padmaja K. Rani Ramesh Kekunnaya Preeti Patil Chhablani Subhabrata Chakrabarti Inderjeet Kaur An interplay of microglia and matrix metalloproteinase MMP9 under hypoxic stress regulates the opticin expression in retina |
| description |
Abstract Inflammation plays a key role in the pathogenesis of retinal vascular diseases. We have shown earlier an increase in the activity of matrix metalloproteinases in the vitreous and tears of preterm born babies with retinopathy of prematurity (ROP) compared to those with no-ROP leading to a shift in the balance of angiogenic (vascular endothelial growth factor [VEGF], matrix metalloproteinase [MMPs], complement component [C3]) and anti-angiogenic (opticin, thrombospondin) in ROP eyes. We now confirmed that tear MMP levels in premature infants perfectly correlates with disease severity. Next, we demonstrated that a reduced opticin levels in ROP vitreous are regulated by MMPs secreted by activated microglia. Upon exposing the human microglia cell line (CHME3) to hypoxia, an increased expression of inflammatory proteins (MMP9, VEGF) was noticed while opticin reduced significantly (p = 0.005). Further, the reduced opticin’s expression by microglial cells under hypoxia could be rescued by inhibiting the MMP activity using doxycycline and EDTA. The inhibition of MMP activity altered the expression of other key signaling molecules under hypoxia. Our study clearly explains that increased activity of MMPs under hypoxia regulates the expression of opticin as seen in the vitreous humor of ROP and could serve as a potential target for ROP management. |
| format |
article |
| author |
Satish Patnaik Meenakshi Rai Subhadra Jalali Komal Agarwal Akshay Badakere Lavanya Puppala Sushma Vishwakarma Divya Balakrishnan Padmaja K. Rani Ramesh Kekunnaya Preeti Patil Chhablani Subhabrata Chakrabarti Inderjeet Kaur |
| author_facet |
Satish Patnaik Meenakshi Rai Subhadra Jalali Komal Agarwal Akshay Badakere Lavanya Puppala Sushma Vishwakarma Divya Balakrishnan Padmaja K. Rani Ramesh Kekunnaya Preeti Patil Chhablani Subhabrata Chakrabarti Inderjeet Kaur |
| author_sort |
Satish Patnaik |
| title |
An interplay of microglia and matrix metalloproteinase MMP9 under hypoxic stress regulates the opticin expression in retina |
| title_short |
An interplay of microglia and matrix metalloproteinase MMP9 under hypoxic stress regulates the opticin expression in retina |
| title_full |
An interplay of microglia and matrix metalloproteinase MMP9 under hypoxic stress regulates the opticin expression in retina |
| title_fullStr |
An interplay of microglia and matrix metalloproteinase MMP9 under hypoxic stress regulates the opticin expression in retina |
| title_full_unstemmed |
An interplay of microglia and matrix metalloproteinase MMP9 under hypoxic stress regulates the opticin expression in retina |
| title_sort |
interplay of microglia and matrix metalloproteinase mmp9 under hypoxic stress regulates the opticin expression in retina |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/a0957f7a3b37412eb9e936c5d954316e |
| work_keys_str_mv |
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