The role of PCSK9 in glomerular lipid accumulation and renal injury in diabetic kidney disease
Year: 2019
Type: dissertation
Abstract: Background: Glomerular lipid accumulation is one of the pathologic characteristics of diabetic kidney disease (DKD). Recent evidences have suggested the specific role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in cellular lipid homeostasis. Herein, I evaluate the role of PCSK9 in lipid accumulation in glomeruli and podocytes under diabetic condition. Methods: C57BL/6 and PCSK9 knockout mice were fed with high fat diet and intraperitoneally injected with low dose streptozotocin for 12 weeks. Lipid accumulation in the kidney tissue was confirmed with BODIPY 493/503 staining. Upregulation or downregulation of PCSK9 expression in mouse podocytes was mediated by lentivirus or small�밿nterfering RNA (siRNA) in the presence of various treatments. Apoptosis, mitochondrial morphology, and the key factors related to energy metabolism were evaluated both in vivo and in vitro. Results: Lipid accumulation was significant in the kidney tissues from DKD with PCSK9 knockout as compared to control and DKD only mice. Mitochondrial morphology and the expression of metabolic enzymes were disturbed in PCSK9 knockout mice. Intracellular lipid accumulation and apoptosis along with mitochondrial swelling and crista disruption increased in the podocytes after treatment. These changes ameliorated after PCSK9 overexpression but aggravated after siRNA�뱈edicated knockdown of PCSK9 expression. Conclusion: These findings suggest that PCSK9 down�뱑egulation in podocytes may be related to lipid accumulation and renal injury through mitochondrial dysfunction and apoptosis in DKD.\n\n諛곌꼍: �궗援ъ껜 吏�吏� 異뺤쟻�� �떦�눊蹂묒꽦 �떊利앹쓽 蹂묐━�븰�쟻�씤 �듅吏� 媛��슫�뜲 �븯�굹�씠�떎. 理쒓렐 �뿰援щ�� �넻�빐 proprotein convertase subtilisin/kexin type 9 (PCSK9)�씠 �꽭�룷 吏�吏� 議곗젅�뿉 以묒슂�븳 �뿭�븷�쓣 �븯�뒗 寃껋쑝濡� �븣�젮吏�怨� �엳�떎. 紐⑹쟻: 蹂� �뿰援щ�� �넻�븯�뿬 �떦�눊蹂묒꽦 �떊利앹뿉�꽌 PCSK9�씠 �궗援ъ껜 諛� 議깆꽭�룷 吏�吏� 異뺤쟻 諛� �넀�긽 怨쇱젙�뿉 �뼱�뼚�븳 �뿭�븷�쓣 �븯�뒗吏� �븣�븘蹂닿퀬�옄 �븯���떎. 諛⑸쾿: C57BL/6�� PCSK9 諛쒗쁽�쓣 �젣嫄고븳 伊먯뿉寃� 怨좎�諛⑹떇�씠 諛� 12二쇨컙�쓽 ���냽�룄 streptozotocin 蹂듦컯�궡 �닾�뿬瑜� �넻�븯�뿬 2�삎 �떦�눊瑜� �쑀諛쒗븯���떎. �떊�옣�궡 吏�吏� 異뺤쟻�� BODIPY 493/503 �뿼�깋�쓣 �넻�븯�뿬 �솗�씤�븯���떎. 伊� 議깆꽭�룷瑜� �씠�슜�븳 �떎�뼇�븳 �옄洹� �떎�뿕�뿉�꽌 PCSK9 諛쒗쁽�쓽 利앷� 諛� ���븯�뿉 ���븳 議곗젅�� lentivirus �삉�뒗 small�밿nterfering RNA (siRNA)瑜� �넻�븯�뿬 吏꾪뻾�븯���떎. �꽭�룷�궗硫�, 誘명넗肄섎뱶由ъ븘 �삎�깭 蹂��솕, 諛� �뿉�꼫吏� ���궗�� 愿��젴�맂 二쇱슂 �씤�옄�뱾�쓽 蹂��솕瑜� 泥대궡 諛� 泥댁쇅 �떎�뿕�쓣 �넻�븯�뿬 �솗�씤�븯���떎. 寃곌낵: ��議곌뎔�씠�굹 �떦�눊蹂묒꽦�떊利앹쓣 媛�吏�怨� �엳�뒗 伊먯뿉 鍮꾪븯�뿬 PCSK9 諛쒗쁽�씠 �젣嫄곕맂 �떦�눊蹂묒꽦�떊利� 伊먯쓽 �떊�옣�뿉�꽌 吏�吏� 異뺤쟻�쓽 利앷�媛� 愿�李곕릺�뿀�떎. �삉�븳, PCSK9 諛쒗쁽�씠 �젣嫄곕맂 伊먯뿉�꽌 誘명넗肄섎뱶由ъ븘 紐⑥뼇怨� �뿉�꼫吏� ���궗�� 愿��젴�맂 �떒諛깆쭏�뱾�쓽 蹂��삎�씠 愿�李곕릺�뿀�떎. 議깆꽭�룷瑜� �씠�슜�븳 �꽭�룷 �떎�뿕�뿉�꽌 �떦�눊 �옄洹뱀뿉 �쓽�븯�뿬 誘명넗肄섎뱶由ъ븘�쓽 �뙺李� 諛� �뙆愿� �냼寃ъ씠 �룞諛섎맂 �꽭�룷�궡 吏�吏� 異뺤쟻 諛� �꽭�룷�궗硫� �냼寃ъ씠 愿�李곕릺�뿀�떎. �씠�윭�븳 蹂��솕�뱾�� PCSK9 諛쒗쁽�쓣 利앷��떆�궎�뒗 寃쎌슦 �샇�쟾�릺�뿀怨�, siRNA濡� 諛쒗쁽�쓣 媛먯냼�떆�궎�뒗 寃쎌슦 �븙�솕�릺�뿀�떎. 寃곕줎: �씠�긽�쓽 寃곌낵瑜� 醫낇빀�븯�뿬 蹂� �븣, �떦�눊蹂묒꽦 �떊利앹뿉�꽌 議깆꽭�룷�쓽 PCSK9 諛쒗쁽 媛먯냼�뒗 誘명넗肄섎뱶由ъ븘�쓽 �넀�긽 諛� �꽭�룷�궗硫몄쓣 �넻�븯�뿬 吏�吏� 異뺤쟻怨� �떊�넀�긽�쓣 �씪�쑝�궎�뒗 寃껋뿉 愿��뿬�븯�뒗 寃껋쑝濡� �깮媛곷맂�떎.
Author: 윤창연
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3042893346